Skip to main content

Tight Junctions in the Inflamed Gut

  • Chapter
  • First Online:
Tight Junctions

Abstract

The gastrointestinal system digests and absorbs nutrients while integrating exogenous and endogenous signals that contribute to create immune tolerance. Epithelial cells forming the physical barrier regulate ion, solutes, and water absorption in the gut. Tight junctions (TJs) are specialized cell-cell junctions that bring adjacent gastrointestinal epithelial cells together and seal the paracellular space. Additionally, TJs are important for maintaining cellular polarity in epithelial cells and in the gastrointestinal epithelium itself. Dysfunctional gastrointestinal TJ enhances leakage of luminal contents into the interstitium, a process that stimulates the development of inflammatory disorders. Therefore, the pathophysiology of the TJs has gained attention in the medical field. Several studies aimed to investigate the viability of those structures are now used in the diagnosis for patients with chronic gastrointestinal inflammation. This chapter focuses on analyzing the role of the TJs in the gut, the techniques employed to study these structures, as well as various mechanisms responsible for compromising the TJs and the intestinal epithelial barrier.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AJ:

Adherens junctions

AJC:

Apical junctional complex

CK1:

Casein kinase 1

cPKC:

Ca2+-dependent protein kinase C

ECL1:

First extracellular loop

ECL2:

Second extracellular loop

GI:

Gastrointestinal

GuK:

Guanylate kinase homology

IBD:

Inflammatory bowel disease

IEC:

Intestinal epithelial cells

Ig:

Immunoglobulin

IHC:

Immunohistochemistry

IL:

Interleukin

IP:

Intestinal permeability

JAMs:

Junctional adhesion molecules

KO:

Knockout

MUPP1:

Multi-PDZ domain protein 1

PDZ:

PSD95, DlgA, ZO1 homology

PKA:

Protein kinase A

QIIME:

Quantitative Insights Into Microbial Ecology

SH3:

Non-catalytic SRC homology 3

TJs:

Tight junctions

ZO:

Zonula occludens

References

  1. Kiela, P. R., & Ghishan, F. K. (2016). Physiology of Intestinal Absorption and Secretion. Best Practice & Research. Clinical Gastroenterology, 30(2), 145-159. https://doi.org/10.1016/j.bpg.2016.02.007

    Article  CAS  Google Scholar 

  2. Cheng, L. K., O’Grady, G., Du, P., Egbuji, J. U., Windsor, J. A., & Pullan, A. J. (2010). Gastrointestinal system. Wiley Interdisciplinary Reviews. Systems Biology and Medicine, 2(1), 65-79. https://doi.org/10.1002/wsbm.19

    Article  PubMed  PubMed Central  Google Scholar 

  3. Kararli, T. T. (1995). Comparison of the gastrointestinal anatomy, physiology, and biochemistry of humans and commonly used laboratory animals. Biopharmaceutics & Drug Disposition, 16(5), 351-380. https://doi.org/10.1002/bdd.2510160502

    Article  CAS  Google Scholar 

  4. Cereijido, M., Contreras, R. G., & Shoshani, L. (2004). Cell adhesion, polarity, and epithelia in the dawn of metazoans. Physiological Reviews, 84(4), 1229-1262. https://doi.org/10.1152/physrev.00001.2004

    Article  CAS  PubMed  Google Scholar 

  5. Farquhar, M. G., & Palade, G. E. (1963). Junctional complexes in various epithelia. The Journal of Cell Biology, 17, 375-412. https://doi.org/10.1083/jcb.17.2.375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Gumber, S., Nusrat, A., & Villinger, F. (2014). Immunohistological characterization of intercellular junction proteins in rhesus macaque intestine. Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Fur Toxikologische Pathologie, 66(9-10), 437-444. https://doi.org/10.1016/j.etp.2014.07.004

    Article  CAS  Google Scholar 

  7. Madara, J. L., Nash, S., Moore, R., & Atisook, K. (1990). Structure and function of the intestinal epithelial barrier in health and disease. Monographs in Pathology, 31, 306-324.

    Google Scholar 

  8. Furuse, M., Hirase, T., Itoh, M., Nagafuchi, A., Yonemura, S., Tsukita, S., & Tsukita, S. (1993). Occludin: A novel integral membrane protein localizing at tight junctions. The Journal of Cell Biology, 123(6 Pt 2), 1777-1788. https://doi.org/10.1083/jcb.123.6.1777

    Article  CAS  PubMed  Google Scholar 

  9. Tsukita, S., & Furuse, M. (2000). Pores in the wall: Claudins constitute tight junction strands containing aqueous pores. The Journal of Cell Biology, 149(1), 13-16. https://doi.org/10.1083/jcb.149.1.13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tsukita, S., Furuse, M., & Itoh, M. (2001). Multifunctional strands in tight junctions. Nature Reviews. Molecular Cell Biology, 2(4), 285-293. https://doi.org/10.1038/35067088

    Article  CAS  PubMed  Google Scholar 

  11. Martini, E., Krug, S. M., Siegmund, B., Neurath, M. F., & Becker, C. (2017). Mend Your Fences: The Epithelial Barrier and its Relationship With Mucosal Immunity in Inflammatory Bowel Disease. Cellular and Molecular Gastroenterology and Hepatology, 4(1), 33-46. https://doi.org/10.1016/j.jcmgh.2017.03.007

    Article  PubMed  PubMed Central  Google Scholar 

  12. Somsouk, M., Estes, J. D., Deleage, C., Dunham, R. M., Albright, R., Inadomi, J. M., Martin, J. N., Deeks, S. G., McCune, J. M., & Hunt, P. W. (2015). Gut epithelial barrier and systemic inflammation during chronic HIV infection. AIDS (London, England), 29(1), 43-51. https://doi.org/10.1097/QAD.0000000000000511

    Article  CAS  Google Scholar 

  13. Turner, J. R. (2009). Intestinal mucosal barrier function in health and disease. Nature Reviews. Immunology, 9(11), 799-809. https://doi.org/10.1038/nri2653

    Article  CAS  PubMed  Google Scholar 

  14. Crosnier, C., Stamataki, D., & Lewis, J. (2006). Organizing cell renewal in the intestine: Stem cells, signals and combinatorial control. Nature Reviews. Genetics, 7(5), 349-359. https://doi.org/10.1038/nrg1840

    Article  CAS  PubMed  Google Scholar 

  15. Rees, W. D., Tandun, R., Yau, E., Zachos, N. C., & Steiner, T. S. (2020). Regenerative Intestinal Stem Cells Induced by Acute and Chronic Injury: The Saving Grace of the Epithelium? Frontiers in Cell and Developmental Biology, 8, 583919. https://doi.org/10.3389/fcell.2020.583919

    Article  PubMed  PubMed Central  Google Scholar 

  16. Sato, T., Vries, R. G., Snippert, H. J., van de Wetering, M., Barker, N., Stange, D. E., van Es, J. H., Abo, A., Kujala, P., Peters, P. J., & Clevers, H. (2009). Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature, 459(7244), 262-265. https://doi.org/10.1038/nature07935

    Article  CAS  PubMed  Google Scholar 

  17. Camilleri, M., Madsen, K., Spiller, R., Greenwood-Van Meerveld, B., Van Meerveld, B. G., & Verne, G. N. (2012). Intestinal barrier function in health and gastrointestinal disease. Neurogastroenterology and Motility: The Official Journal of the European Gastrointestinal Motility Society, 24(6), 503-512. https://doi.org/10.1111/j.1365-2982.2012.01921.x

    Article  CAS  Google Scholar 

  18. Bischoff, S. C., Barbara, G., Buurman, W., Ockhuizen, T., Schulzke, J.-D., Serino, M., Tilg, H., Watson, A., & Wells, J. M. (2014). Intestinal permeability—A new target for disease prevention and therapy. BMC Gastroenterology, 14, 189. https://doi.org/10.1186/s12876-014-0189-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Schulzke, J. D., Schulzke, I., Fromm, M., & Riecken, E. O. (1995). Epithelial barrier and ion transport in coeliac sprue: Electrical measurements on intestinal aspiration biopsy specimens. Gut, 37(6), 777-782. https://doi.org/10.1136/gut.37.6.777

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Karasov, W. H. (2017). Integrative physiology of transcellular and paracellular intestinal absorption. The Journal of Experimental Biology, 220(Pt 14), 2495-2501. https://doi.org/10.1242/jeb.144048

    Article  PubMed  Google Scholar 

  21. Camilleri, M., Nadeau, A., Lamsam, J., Nord, S. L., Ryks, M., Burton, D., Sweetser, S., Zinsmeister, A. R., & Singh, R. (2010). Understanding measurements of intestinal permeability in healthy humans with urine lactulose and mannitol excretion. Neurogastroenterology and Motility: The Official Journal of the European Gastrointestinal Motility Society, 22(1), e15-26. https://doi.org/10.1111/j.1365-2982.2009.01361.x

    Article  CAS  Google Scholar 

  22. Fung, K. Y. Y., Fairn, G. D., & Lee, W. L. (2018). Transcellular vesicular transport in epithelial and endothelial cells: Challenges and opportunities. Traffic (Copenhagen, Denmark), 19(1), 5-18. https://doi.org/10.1111/tra.12533

    Article  CAS  Google Scholar 

  23. Kellett, G. L., Brot-Laroche, E., Mace, O. J., & Leturque, A. (2008). Sugar absorption in the intestine: The role of GLUT2. Annual Review of Nutrition, 28, 35-54. https://doi.org/10.1146/annurev.nutr.28.061807.155518

    Article  CAS  PubMed  Google Scholar 

  24. Ménard, S., Cerf-Bensussan, N., & Heyman, M. (2010). Multiple facets of intestinal permeability and epithelial handling of dietary antigens. Mucosal Immunology, 3(3), 247-259. https://doi.org/10.1038/mi.2010.5

    Article  CAS  PubMed  Google Scholar 

  25. New, R. (2020). Oral Delivery of Biologics via the Intestine. Pharmaceutics, 13(1), E18. https://doi.org/10.3390/pharmaceutics13010018

    Article  CAS  PubMed  Google Scholar 

  26. Sesorova, I. S., Dimov, I. D., Kashin, A. D., Sesorov, V. V., Karelina, N. R., Zdorikova, M. A., Beznoussenko, G. V., & Mirоnоv, A. A. (2021). Cellular and sub-cellular mechanisms of lipid transport from gut to lymph. Tissue & Cell, 72, 101529. https://doi.org/10.1016/j.tice.2021.101529

    Article  CAS  Google Scholar 

  27. Tamura, A., & Tsukita, S. (2014). Paracellular barrier and channel functions of TJ claudins in organizing biological systems: Advances in the field of barriology revealed in knockout mice. Seminars in Cell & Developmental Biology, 36, 177-185. https://doi.org/10.1016/j.semcdb.2014.09.019

    Article  CAS  Google Scholar 

  28. Tsukita, S., Tanaka, H., & Tamura, A. (2019b). The Claudins: From Tight Junctions to Biological Systems. Trends in Biochemical Sciences, 44(2), 141-152. https://doi.org/10.1016/j.tibs.2018.09.008

    Article  CAS  PubMed  Google Scholar 

  29. González-Mariscal, L., Betanzos, A., Nava, P., & Jaramillo, B. E. (2003). Tight junction proteins. Progress in Biophysics and Molecular Biology, 81(1), 1-44. https://doi.org/10.1016/s0079-6107(02)00037-8

    Article  PubMed  Google Scholar 

  30. Kostrewa, D., Brockhaus, M., D’Arcy, A., Dale, G. E., Nelboeck, P., Schmid, G., Mueller, F., Bazzoni, G., Dejana, E., Bartfai, T., Winkler, F. K., & Hennig, M. (2001). X-ray structure of junctional adhesion molecule: Structural basis for homophilic adhesion via a novel dimerization motif. The EMBO Journal, 20(16), 4391-4398. https://doi.org/10.1093/emboj/20.16.4391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Krause, G., Winkler, L., Mueller, S. L., Haseloff, R. F., Piontek, J., & Blasig, I. E. (2008). Structure and function of claudins. Biochimica Et Biophysica Acta, 1778(3), 631-645. https://doi.org/10.1016/j.bbamem.2007.10.018

    Article  CAS  PubMed  Google Scholar 

  32. González-Mariscal, L., Betanzos, A., & Avila-Flores, A. (2000). MAGUK proteins: Structure and role in the tight junction. Seminars in Cell & Developmental Biology, 11(4), 315-324. https://doi.org/10.1006/scdb.2000.0178

    Article  CAS  Google Scholar 

  33. Otani, T., & Furuse, M. (2020). Tight Junction Structure and Function Revisited. Trends in Cell Biology, 30(10), 805-817. https://doi.org/10.1016/j.tcb.2020.08.004

    Article  CAS  PubMed  Google Scholar 

  34. Citi, S. (2019). The mechanobiology of tight junctions. Biophysical Reviews, 11(5), 783-793. https://doi.org/10.1007/s12551-019-00582-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Mitic, L. L., & Anderson, J. M. (1998). Molecular architecture of tight junctions. Annual Review of Physiology, 60, 121-142. https://doi.org/10.1146/annurev.physiol.60.1.121

    Article  CAS  PubMed  Google Scholar 

  36. Rodgers, L. S., & Fanning, A. S. (2011). Regulation of epithelial permeability by the actin cytoskeleton. Cytoskeleton (Hoboken, N.J.), 68(12), 653-660. https://doi.org/10.1002/cm.20547

    Article  CAS  Google Scholar 

  37. Heinemann, U., & Schuetz, A. (2019). Structural Features of Tight-Junction Proteins. International Journal of Molecular Sciences, 20(23), E6020. https://doi.org/10.3390/ijms20236020

    Article  CAS  PubMed  Google Scholar 

  38. Morita, K., Furuse, M., Fujimoto, K., & Tsukita, S. (1999). Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands. Proceedings of the National Academy of Sciences of the United States of America, 96(2), 511-516. https://doi.org/10.1073/pnas.96.2.511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Daugherty, B. L., Ward, C., Smith, T., Ritzenthaler, J. D., & Koval, M. (2007). Regulation of heterotypic claudin compatibility. The Journal of Biological Chemistry, 282(41), 30005-30013. https://doi.org/10.1074/jbc.M703547200

    Article  CAS  PubMed  Google Scholar 

  40. Piontek, J., Winkler, L., Wolburg, H., Müller, S. L., Zuleger, N., Piehl, C., Wiesner, B., Krause, G., & Blasig, I. E. (2008). Formation of tight junction: Determinants of homophilic interaction between classic claudins. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 22(1), 146-158. https://doi.org/10.1096/fj.07-8319com

    Article  CAS  Google Scholar 

  41. Colegio, O. R., Van Itallie, C., Rahner, C., & Anderson, J. M. (2003). Claudin extracellular domains determine paracellular charge selectivity and resistance but not tight junction fibril architecture. American Journal of Physiology. Cell Physiology, 284(6), C1346-1354. https://doi.org/10.1152/ajpcell.00547.2002

    Article  CAS  PubMed  Google Scholar 

  42. Suzuki, H., Nishizawa, T., Tani, K., Yamazaki, Y., Tamura, A., Ishitani, R., Dohmae, N., Tsukita, S., Nureki, O., & Fujiyoshi, Y. (2014). Crystal structure of a claudin provides insight into the architecture of tight junctions. Science (New York, N.Y.), 344(6181), 304-307. https://doi.org/10.1126/science.1248571

    Article  CAS  Google Scholar 

  43. Reiche, J., & Huber, O. (2020). Post-translational modifications of tight junction transmembrane proteins and their direct effect on barrier function. Biochimica Et Biophysica Acta. Biomembranes, 1862(9), 183330. https://doi.org/10.1016/j.bbamem.2020.183330

    Article  CAS  PubMed  Google Scholar 

  44. Van Itallie, C. M., Gambling, T. M., Carson, J. L., & Anderson, J. M. (2005). Palmitoylation of claudins is required for efficient tight-junction localization. Journal of Cell Science, 118(Pt 7), 1427-1436. https://doi.org/10.1242/jcs.01735

    Article  CAS  PubMed  Google Scholar 

  45. Van Itallie, C. M., Mitic, L. L., & Anderson, J. M. (2012). SUMOylation of claudin-2. Annals of the New York Academy of Sciences, 1258, 60-64. https://doi.org/10.1111/j.1749-6632.2012.06541.x

    Article  CAS  PubMed  Google Scholar 

  46. Barmeyer, C., Schulzke, J. D., & Fromm, M. (2015). Claudin-related intestinal diseases. Seminars in Cell & Developmental Biology, 42, 30-38. https://doi.org/10.1016/j.semcdb.2015.05.006

    Article  CAS  Google Scholar 

  47. Fujita, H., Chiba, H., Yokozaki, H., Sakai, N., Sugimoto, K., Wada, T., Kojima, T., Yamashita, T., & Sawada, N. (2006). Differential expression and subcellular localization of claudin-7, -8, -12, -13, and -15 along the mouse intestine. The Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society, 54(8), 933-944. https://doi.org/10.1369/jhc.6A6944.2006

    Article  CAS  Google Scholar 

  48. Garcia-Hernandez, V., Quiros, M., & Nusrat, A. (2017). Intestinal epithelial claudins: Expression and regulation in homeostasis and inflammation. Annals of the New York Academy of Sciences, 1397(1), 66-79. https://doi.org/10.1111/nyas.13360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Holmes, J. L., Van Itallie, C. M., Rasmussen, J. E., & Anderson, J. M. (2006). Claudin profiling in the mouse during postnatal intestinal development and along the gastrointestinal tract reveals complex expression patterns. Gene Expression Patterns: GEP, 6(6), 581-588. https://doi.org/10.1016/j.modgep.2005.12.001

    Article  CAS  PubMed  Google Scholar 

  50. Lameris, A. L., Huybers, S., Kaukinen, K., Mäkelä, T. H., Bindels, R. J., Hoenderop, J. G., & Nevalainen, P. I. (2013). Expression profiling of claudins in the human gastrointestinal tract in health and during inflammatory bowel disease. Scandinavian Journal of Gastroenterology, 48(1), 58-69. https://doi.org/10.3109/00365521.2012.741616

    Article  CAS  PubMed  Google Scholar 

  51. Nakagawa, S., Miyoshi, N., Ishii, H., Mimori, K., Tanaka, F., Sekimoto, M., Doki, Y., & Mori, M. (2011). Expression of CLDN1 in colorectal cancer: A novel marker for prognosis. International Journal of Oncology, 39(4), 791-796. https://doi.org/10.3892/ijo.2011.1102

    Article  CAS  PubMed  Google Scholar 

  52. Yoshida, T., Kinugasa, T., Akagi, Y., Kawahara, A., Romeo, K., Shiratsuchi, I., Ryu, Y., Gotanda, Y., & Shirouzu, K. (2011). Decreased expression of claudin-1 in rectal cancer: A factor for recurrence and poor prognosis. Anticancer Research, 31(7), 2517-2525.

    CAS  PubMed  Google Scholar 

  53. Curry, J. N., Saurette, M., Askari, M., Pei, L., Filla, M. B., Beggs, M. R., Rowe, P. S., Fields, T., Sommer, A. J., Tanikawa, C., Kamatani, Y., Evan, A. P., Totonchi, M., Alexander, R. T., Matsuda, K., & Yu, A. S. (2020). Claudin-2 deficiency associates with hypercalciuria in mice and human kidney stone disease. The Journal of Clinical Investigation, 130(4), 1948-1960. https://doi.org/10.1172/JCI127750

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Raju, P., Shashikanth, N., Tsai, P.-Y., Pongkorpsakol, P., Chanez-Paredes, S., Steinhagen, P. R., Kuo, W.-T., Singh, G., Tsukita, S., & Turner, J. R. (2020). Inactivation of paracellular cation-selective claudin-2 channels attenuates immune-mediated experimental colitis in mice. The Journal of Clinical Investigation, 130(10), 5197-5208. https://doi.org/10.1172/JCI138697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Xing, T., Camacho Salazar, R., & Chen, Y.-H. (2017). Animal models for studying epithelial barriers in neonatal necrotizing enterocolitis, inflammatory bowel disease and colorectal cancer. Tissue Barriers, 5(4), e1356901. https://doi.org/10.1080/21688370.2017.1356901

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ding, L., Lu, Z., Foreman, O., Tatum, R., Lu, Q., Renegar, R., Cao, J., & Chen, Y.-H. (2012). Inflammation and disruption of the mucosal architecture in claudin-7-deficient mice. Gastroenterology, 142(2), 305-315. https://doi.org/10.1053/j.gastro.2011.10.025

    Article  CAS  PubMed  Google Scholar 

  57. Tabariès, S., & Siegel, P. M. (2017). The role of claudins in cancer metastasis. Oncogene, 36(9), 1176-1190. https://doi.org/10.1038/onc.2016.289

    Article  CAS  PubMed  Google Scholar 

  58. Tamura, A., Hayashi, H., Imasato, M., Yamazaki, Y., Hagiwara, A., Wada, M., Noda, T., Watanabe, M., Suzuki, Y., & Tsukita, S. (2011). Loss of claudin-15, but not claudin-2, causes Na+ deficiency and glucose malabsorption in mouse small intestine. Gastroenterology, 140(3), 913-923. https://doi.org/10.1053/j.gastro.2010.08.006

    Article  CAS  PubMed  Google Scholar 

  59. Maryan, N., Statkiewicz, M., Mikula, M., Goryca, K., Paziewska, A., Strzałkowska, A., Dabrowska, M., Bujko, M., & Ostrowski, J. (2015). Regulation of the expression of claudin 23 by the enhancer of zeste 2 polycomb group protein in colorectal cancer. Molecular Medicine Reports, 12(1), 728-736. https://doi.org/10.3892/mmr.2015.3378

    Article  CAS  PubMed  Google Scholar 

  60. Tanaka, H., Takechi, M., Kiyonari, H., Shioi, G., Tamura, A., & Tsukita, S. (2015). Intestinal deletion of Claudin-7 enhances paracellular organic solute flux and initiates colonic inflammation in mice. Gut, 64(10), 1529-1538. https://doi.org/10.1136/gutjnl-2014-308419

    Article  CAS  PubMed  Google Scholar 

  61. Fujita, H., Sugimoto, K., Inatomi, S., Maeda, T., Osanai, M., Uchiyama, Y., Yamamoto, Y., Wada, T., Kojima, T., Yokozaki, H., Yamashita, T., Kato, S., Sawada, N., & Chiba, H. (2008). Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes. Molecular Biology of the Cell, 19(5), 1912-1921. https://doi.org/10.1091/mbc.e07-09-0973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Van Itallie, C. M., Fanning, A. S., & Anderson, J. M. (2003). Reversal of charge selectivity in cation or anion-selective epithelial lines by expression of different claudins. American Journal of Physiology. Renal Physiology, 285(6), F1078-1084. https://doi.org/10.1152/ajprenal.00116.2003

    Article  PubMed  Google Scholar 

  63. Cummins, P. M. (2012). Occludin: One protein, many forms. Molecular and Cellular Biology, 32(2), 242-250. https://doi.org/10.1128/MCB.06029-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Feldman, G. J., Mullin, J. M., & Ryan, M. P. (2005). Occludin: Structure, function and regulation. Advanced Drug Delivery Reviews, 57(6), 883-917. https://doi.org/10.1016/j.addr.2005.01.009

    Article  CAS  PubMed  Google Scholar 

  65. Medina, R., Rahner, C., Mitic, L. L., Anderson, J. M., & Van Itallie, C. M. (2000). Occludin localization at the tight junction requires the second extracellular loop. The Journal of Membrane Biology, 178(3), 235-247. https://doi.org/10.1007/s002320010031

    Article  CAS  PubMed  Google Scholar 

  66. Chen, Y., Merzdorf, C., Paul, D. L., & Goodenough, D. A. (1997). COOH terminus of occludin is required for tight junction barrier function in early Xenopus embryos. The Journal of Cell Biology, 138(4), 891-899. https://doi.org/10.1083/jcb.138.4.891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Furuse, M., Itoh, M., Hirase, T., Nagafuchi, A., Yonemura, S., Tsukita, S., & Tsukita, S. (1994). Direct association of occludin with ZO-1 and its possible involvement in the localization of occludin at tight junctions. The Journal of Cell Biology, 127(6 Pt 1), 1617-1626. https://doi.org/10.1083/jcb.127.6.1617

    Article  CAS  PubMed  Google Scholar 

  68. Bamforth, S. D., Kniesel, U., Wolburg, H., Engelhardt, B., & Risau, W. (1999). A dominant mutant of occludin disrupts tight junction structure and function. Journal of Cell Science, 112 ( Pt 12), 1879-1888.

    Article  CAS  Google Scholar 

  69. Muresan, Z., Paul, D. L., & Goodenough, D. A. (2000). Occludin 1B, a variant of the tight junction protein occludin. Molecular Biology of the Cell, 11(2), 627-634. https://doi.org/10.1091/mbc.11.2.627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Al-Sadi, R., Khatib, K., Guo, S., Ye, D., Youssef, M., & Ma, T. (2011). Occludin regulates macromolecule flux across the intestinal epithelial tight junction barrier. American Journal of Physiology. Gastrointestinal and Liver Physiology, 300(6), G1054-1064. https://doi.org/10.1152/ajpgi.00055.2011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Kyoko, O., Kono, H., Ishimaru, K., Miyake, K., Kubota, T., Ogawa, H., Okumura, K., Shibata, S., & Nakao, A. (2014). Expressions of tight junction proteins Occludin and Claudin-1 are under the circadian control in the mouse large intestine: Implications in intestinal permeability and susceptibility to colitis. PloS One, 9(5), e98016. https://doi.org/10.1371/journal.pone.0098016

    Article  CAS  PubMed  Google Scholar 

  72. Dörfel, M. J., Westphal, J. K., Bellmann, C., Krug, S. M., Cording, J., Mittag, S., Tauber, R., Fromm, M., Blasig, I. E., & Huber, O. (2013). CK2-dependent phosphorylation of occludin regulates the interaction with ZO-proteins and tight junction integrity. Cell Communication and Signaling: CCS, 11(1), 40. https://doi.org/10.1186/1478-811X-11-40

    Article  CAS  PubMed Central  Google Scholar 

  73. Kuo, W.-T., Shen, L., Zuo, L., Shashikanth, N., Ong, M. L. D. M., Wu, L., Zha, J., Edelblum, K. L., Wang, Y., Wang, Y., Nilsen, S. P., & Turner, J. R. (2019). Inflammation-induced Occludin Downregulation Limits Epithelial Apoptosis by Suppressing Caspase-3 Expression. Gastroenterology, 157(5), 1323-1337. https://doi.org/10.1053/j.gastro.2019.07.058

    Article  CAS  PubMed  Google Scholar 

  74. Hanning, N., Edwinson, A. L., Ceuleers, H., Peters, S. A., De Man, J. G., Hassett, L. C., De Winter, B. Y., & Grover, M. (2021). Intestinal barrier dysfunction in irritable bowel syndrome: A systematic review. Therapeutic Advances in Gastroenterology, 14, 1756284821993586. https://doi.org/10.1177/1756284821993586

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Martínez, C., Lobo, B., Pigrau, M., Ramos, L., González-Castro, A. M., Alonso, C., Guilarte, M., Guilá, M., de Torres, I., Azpiroz, F., Santos, J., & Vicario, M. (2013). Diarrhoea-predominant irritable bowel syndrome: An organic disorder with structural abnormalities in the jejunal epithelial barrier. Gut, 62(8), 1160-1168. https://doi.org/10.1136/gutjnl-2012-302093

    Article  CAS  PubMed  Google Scholar 

  76. Annaházi, A., Ferrier, L., Bézirard, V., Lévêque, M., Eutamène, H., Ait-Belgnaoui, A., Coëffier, M., Ducrotté, P., Róka, R., Inczefi, O., Gecse, K., Rosztóczy, A., Molnár, T., Ringel-Kulka, T., Ringel, Y., Piche, T., Theodorou, V., Wittmann, T., & Bueno, L. (2013). Luminal cysteine-proteases degrade colonic tight junction structure and are responsible for abdominal pain in constipation-predominant IBS. The American Journal of Gastroenterology, 108(8), 1322-1331. https://doi.org/10.1038/ajg.2013.152

    Article  CAS  PubMed  Google Scholar 

  77. Oshitani, N., Watanabe, K., Nakamura, S., Fujiwara, Y., Higuchi, K., & Arakawa, T. (2005). Dislocation of tight junction proteins without F-actin disruption in inactive Crohn’s disease. International Journal of Molecular Medicine, 15(3), 407-410.

    CAS  PubMed  Google Scholar 

  78. Yamamoto-Furusho, J. K., Mendivil, E. J., Mendivil-Rangel, E. J., & Fonseca-Camarillo, G. (2012). Differential expression of occludin in patients with ulcerative colitis and healthy controls. Inflammatory Bowel Diseases, 18(10), E1999. https://doi.org/10.1002/ibd.22835

    Article  PubMed  Google Scholar 

  79. Zeissig, S., Bürgel, N., Günzel, D., Richter, J., Mankertz, J., Wahnschaffe, U., Kroesen, A. J., Zeitz, M., Fromm, M., & Schulzke, J.-D. (2007). Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn’s disease. Gut, 56(1), 61-72. https://doi.org/10.1136/gut.2006.094375

    Article  CAS  PubMed  Google Scholar 

  80. Bürgel, N., Bojarski, C., Mankertz, J., Zeitz, M., Fromm, M., & Schulzke, J.-D. (2002). Mechanisms of diarrhea in collagenous colitis. Gastroenterology, 123(2), 433-443. https://doi.org/10.1053/gast.2002.34784

    Article  PubMed  Google Scholar 

  81. Krug, S. M., Schulzke, J. D., & Fromm, M. (2014). Tight junction, selective permeability, and related diseases. Seminars in Cell & Developmental Biology, 36, 166-176. https://doi.org/10.1016/j.semcdb.2014.09.002

    Article  CAS  Google Scholar 

  82. Shen, L., & Turner, J. R. (2005). Actin depolymerization disrupts tight junctions via caveolae-mediated endocytosis. Molecular Biology of the Cell, 16(9), 3919-3936. https://doi.org/10.1091/mbc.e04-12-1089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Utech, M., Ivanov, A. I., Samarin, S. N., Bruewer, M., Turner, J. R., Mrsny, R. J., Parkos, C. A., & Nusrat, A. (2005). Mechanism of IFN-gamma-induced endocytosis of tight junction proteins: Myosin II-dependent vacuolarization of the apical plasma membrane. Molecular Biology of the Cell, 16(10), 5040-5052. https://doi.org/10.1091/mbc.e05-03-0193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Youakim, A., & Ahdieh, M. (1999). Interferon-gamma decreases barrier function in T84 cells by reducing ZO-1 levels and disrupting apical actin. The American Journal of Physiology, 276(5), G1279-1288. https://doi.org/10.1152/ajpgi.1999.276.5.G1279

    Article  CAS  PubMed  Google Scholar 

  85. Liu, H., Li, M., Wang, P., & Wang, F. (2011). Blockade of hypoxia-inducible factor-1α by YC-1 attenuates interferon-γ and tumor necrosis factor-α-induced intestinal epithelial barrier dysfunction. Cytokine, 56(3), 581-588. https://doi.org/10.1016/j.cyto.2011.08.023

    Article  CAS  PubMed  Google Scholar 

  86. Ogawa, M., Osada, H., Hasegawa, A., Ohno, H., Yanuma, N., Sasaki, K., Shimoda, M., Shirai, J., Kondo, H., & Ohmori, K. (2018). Effect of interleukin-1β on occludin mRNA expression in the duodenal and colonic mucosa of dogs with inflammatory bowel disease. Journal of Veterinary Internal Medicine, 32(3), 1019-1025. https://doi.org/10.1111/jvim.15117

    Article  PubMed  PubMed Central  Google Scholar 

  87. Wang, X., Zeng, H.-C., Huang, Y.-R., & He, Q.-Z. (2020b). Chlamydia muridarum Alleviates Colitis via the IL-22/Occludin Signal Pathway. BioMed Research International, 2020, 8894331. https://doi.org/10.1155/2020/8894331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Wiley, J. W., Zong, Y., Zheng, G., Zhu, S., & Hong, S. (2020). Histone H3K9 methylation regulates chronic stress and IL-6-induced colon epithelial permeability and visceral pain. Neurogastroenterology and Motility: The Official Journal of the European Gastrointestinal Motility Society, 32(12), e13941. https://doi.org/10.1111/nmo.13941

    Article  CAS  Google Scholar 

  89. Minagar, A., Long, A., Ma, T., Jackson, T. H., Kelley, R. E., Ostanin, D. V., Sasaki, M., Warren, A. C., Jawahar, A., Cappell, B., & Alexander, J. S. (2003). Interferon (IFN)-beta 1a and IFN-beta 1b block IFN-gamma-induced disintegration of endothelial junction integrity and barrier. Endothelium: Journal of Endothelial Cell Research, 10(6), 299-307. https://doi.org/10.1080/10623320390272299

    Article  CAS  Google Scholar 

  90. Lee, J. S., Tato, C. M., Joyce-Shaikh, B., Gulen, M. F., Cayatte, C., Chen, Y., Blumenschein, W. M., Judo, M., Ayanoglu, G., McClanahan, T. K., Li, X., & Cua, D. J. (2015). Interleukin-23-Independent IL-17 Production Regulates Intestinal Epithelial Permeability. Immunity, 43(4), 727-738. https://doi.org/10.1016/j.immuni.2015.09.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Díaz-Coránguez, M., Liu, X., & Antonetti, D. A. (2019). Tight Junctions in Cell Proliferation. International Journal of Molecular Sciences, 20(23), E5972. https://doi.org/10.3390/ijms20235972

    Article  CAS  PubMed  Google Scholar 

  92. Yaffe, Y., Shepshelovitch, J., Nevo-Yassaf, I., Yeheskel, A., Shmerling, H., Kwiatek, J. M., Gaus, K., Pasmanik-Chor, M., & Hirschberg, K. (2012). The MARVEL transmembrane motif of occludin mediates oligomerization and targeting to the basolateral surface in epithelia. Journal of Cell Science, 125(Pt 15), 3545-3556. https://doi.org/10.1242/jcs.100289

    Article  CAS  PubMed  Google Scholar 

  93. Raleigh, D. R., Marchiando, A. M., Zhang, Y., Shen, L., Sasaki, H., Wang, Y., Long, M., & Turner, J. R. (2010). Tight junction-associated MARVEL proteins marveld3, tricellulin, and occludin have distinct but overlapping functions. Molecular Biology of the Cell, 21(7), 1200-1213. https://doi.org/10.1091/mbc.e09-08-0734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Bauer, H., Stelzhammer, W., Fuchs, R., Weiger, T. M., Danninger, C., Probst, G., & Krizbai, I. A. (1999). Astrocytes and neurons express the tight junction-specific protein occludin in vitro. Experimental Cell Research, 250(2), 434-438. https://doi.org/10.1006/excr.1999.4558

    Article  CAS  PubMed  Google Scholar 

  95. Castro, V., Skowronska, M., Lombardi, J., He, J., Seth, N., Velichkovska, M., & Toborek, M. (2018). Occludin regulates glucose uptake and ATP production in pericytes by influencing AMP-activated protein kinase activity. Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism, 38(2), 317-332. https://doi.org/10.1177/0271678X17720816

    Article  CAS  Google Scholar 

  96. Morgan, S. V., Garwood, C. J., Jennings, L., Simpson, J. E., Castelli, L. M., Heath, P. R., Mihaylov, S. R., Vaquéz-Villaseñor, I., Minshull, T. C., Ince, P. G., Dickman, M. J., Hautbergue, G. M., & Wharton, S. B. (2018). Proteomic and cellular localisation studies suggest non-tight junction cytoplasmic and nuclear roles for occludin in astrocytes. The European Journal of Neuroscience, 47(12), 1444-1456. https://doi.org/10.1111/ejn.13933

    Article  PubMed  PubMed Central  Google Scholar 

  97. Rescigno, M., Urbano, M., Valzasina, B., Francolini, M., Rotta, G., Bonasio, R., Granucci, F., Kraehenbuhl, J. P., & Ricciardi-Castagnoli, P. (2001). Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nature Immunology, 2(4), 361-367. https://doi.org/10.1038/86373

    Article  CAS  PubMed  Google Scholar 

  98. Saitou, M., Furuse, M., Sasaki, H., Schulzke, J. D., Fromm, M., Takano, H., Noda, T., & Tsukita, S. (2000). Complex phenotype of mice lacking occludin, a component of tight junction strands. Molecular Biology of the Cell, 11(12), 4131-4142. https://doi.org/10.1091/mbc.11.12.4131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Castro, V., Bertrand, L., Luethen, M., Dabrowski, S., Lombardi, J., Morgan, L., Sharova, N., Stevenson, M., Blasig, I. E., & Toborek, M. (2016). Occludin controls HIV transcription in brain pericytes via regulation of SIRT-1 activation. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 30(3), 1234-1246. https://doi.org/10.1096/fj.15-277673

    Article  CAS  Google Scholar 

  100. Martìn-Padura, I., Lostaglio, S., Schneemann, M., Williams, L., Romano, M., Fruscella, P., Panzeri, C., Stoppacciaro, A., Ruco, L., Villa, A., Simmons, D., & Dejana, E. (1998). Junctional adhesion molecule, a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration. The Journal of Cell Biology, 142(1), 117-127. https://doi.org/10.1083/jcb.142.1.117

    Article  PubMed  PubMed Central  Google Scholar 

  101. Ebnet, K., Suzuki, A., Ohno, S., & Vestweber, D. (2004). Junctional adhesion molecules (JAMs): More molecules with dual functions? Journal of Cell Science, 117(Pt 1), 19-29. https://doi.org/10.1242/jcs.00930

    Article  CAS  PubMed  Google Scholar 

  102. Hartmann, C., Schwietzer, Y. A., Otani, T., Furuse, M., & Ebnet, K. (2020). Physiological functions of junctional adhesion molecules (JAMs) in tight junctions. Biochimica Et Biophysica Acta. Biomembranes, 1862(9), 183299. https://doi.org/10.1016/j.bbamem.2020.183299

    Article  CAS  PubMed  Google Scholar 

  103. Luissint, A.-C., Nusrat, A., & Parkos, C. A. (2014). JAM-related proteins in mucosal homeostasis and inflammation. Seminars in Immunopathology, 36(2), 211-226. https://doi.org/10.1007/s00281-014-0421-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Mandell, K. J., & Parkos, C. A. (2005). The JAM family of proteins. Advanced Drug Delivery Reviews, 57(6), 857-867. https://doi.org/10.1016/j.addr.2005.01.005

    Article  CAS  PubMed  Google Scholar 

  105. Steinbacher, T., Kummer, D., & Ebnet, K. (2018). Junctional adhesion molecule-A: Functional diversity through molecular promiscuity. Cellular and Molecular Life Sciences: CMLS, 75(8), 1393-1409. https://doi.org/10.1007/s00018-017-2729-0

    Article  CAS  PubMed  Google Scholar 

  106. Bazzoni, G., Martinez-Estrada, O. M., Orsenigo, F., Cordenonsi, M., Citi, S., & Dejana, E. (2000). Interaction of junctional adhesion molecule with the tight junction components ZO-1, cingulin, and occludin. The Journal of Biological Chemistry, 275(27), 20520-20526. https://doi.org/10.1074/jbc.M905251199

    Article  CAS  PubMed  Google Scholar 

  107. Monteiro, A. C., Sumagin, R., Rankin, C. R., Leoni, G., Mina, M. J., Reiter, D. M., Stehle, T., Dermody, T. S., Schaefer, S. A., Hall, R. A., Nusrat, A., & Parkos, C. A. (2013). JAM-A associates with ZO-2, afadin, and PDZ-GEF1 to activate Rap2c and regulate epithelial barrier function. Molecular Biology of the Cell, 24(18), 2849-2860. https://doi.org/10.1091/mbc.E13-06-0298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Van Itallie, C. M., & Anderson, J. M. (2018). Phosphorylation of tight junction transmembrane proteins: Many sites, much to do. Tissue Barriers, 6(1), e1382671. https://doi.org/10.1080/21688370.2017.1382671

    Article  CAS  PubMed  Google Scholar 

  109. Iden, S., Misselwitz, S., Peddibhotla, S. S. D., Tuncay, H., Rehder, D., Gerke, V., Robenek, H., Suzuki, A., & Ebnet, K. (2012). APKC phosphorylates JAM-A at Ser285 to promote cell contact maturation and tight junction formation. The Journal of Cell Biology, 196(5), 623-639. https://doi.org/10.1083/jcb.201104143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Braiterman, L. T., Heffernan, S., Nyasae, L., Johns, D., See, A. P., Yutzy, R., McNickle, A., Herman, M., Sharma, A., Naik, U. P., & Hubbard, A. L. (2008). JAM-A is both essential and inhibitory to development of hepatic polarity in WIF-B cells. American Journal of Physiology. Gastrointestinal and Liver Physiology, 294(2), G576-588. https://doi.org/10.1152/ajpgi.00159.2007

    Article  CAS  PubMed  Google Scholar 

  111. Naik, M. U., Caplan, J. L., & Naik, U. P. (2014). Junctional adhesion molecule-A suppresses platelet integrin αIIbβ3 signaling by recruiting Csk to the integrin-c-Src complex. Blood, 123(9), 1393-1402. https://doi.org/10.1182/blood-2013-04-496232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Naik, M. U., Mousa, S. A., Parkos, C. A., & Naik, U. P. (2003). Signaling through JAM-1 and alphavbeta3 is required for the angiogenic action of bFGF: Dissociation of the JAM-1 and alphavbeta3 complex. Blood, 102(6), 2108-2114. https://doi.org/10.1182/blood-2003-04-1114

    Article  CAS  PubMed  Google Scholar 

  113. Mandicourt, G., Iden, S., Ebnet, K., Aurrand-Lions, M., & Imhof, B. A. (2007). JAM-C regulates tight junctions and integrin-mediated cell adhesion and migration. The Journal of Biological Chemistry, 282(3), 1830-1837. https://doi.org/10.1074/jbc.M605666200

    Article  CAS  PubMed  Google Scholar 

  114. Morton, P. E., Hicks, A., Nastos, T., Santis, G., & Parsons, M. (2013). CAR regulates epithelial cell junction stability through control of E-cadherin trafficking. Scientific Reports, 3, 2889. https://doi.org/10.1038/srep02889

    Article  PubMed  PubMed Central  Google Scholar 

  115. Nunbhakdi-Craig, V., Machleidt, T., Ogris, E., Bellotto, D., White, C. L., & Sontag, E. (2002). Protein phosphatase 2A associates with and regulates atypical PKC and the epithelial tight junction complex. The Journal of Cell Biology, 158(5), 967-978. https://doi.org/10.1083/jcb.200206114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Fan, S., Weight, C. M., Luissint, A.-C., Hilgarth, R. S., Brazil, J. C., Ettel, M., Nusrat, A., & Parkos, C. A. (2019). Role of JAM-A tyrosine phosphorylation in epithelial barrier dysfunction during intestinal inflammation. Molecular Biology of the Cell, 30(5), 566-578. https://doi.org/10.1091/mbc.E18-08-0531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Shawki, A., & McCole, D. F. (2017). Mechanisms of Intestinal Epithelial Barrier Dysfunction by Adherent-Invasive Escherichia coli. Cellular and Molecular Gastroenterology and Hepatology, 3(1), 41-50. https://doi.org/10.1016/j.jcmgh.2016.10.004

    Article  PubMed  Google Scholar 

  118. Stevenson, B. R., Siliciano, J. D., Mooseker, M. S., & Goodenough, D. A. (1986). Identification of ZO-1: A high molecular weight polypeptide associated with the tight junction (zonula occludens) in a variety of epithelia. The Journal of Cell Biology, 103(3), 755-766. https://doi.org/10.1083/jcb.103.3.755

    Article  CAS  PubMed  Google Scholar 

  119. Jesaitis, L. A., & Goodenough, D. A. (1994). Molecular characterization and tissue distribution of ZO-2, a tight junction protein homologous to ZO-1 and the Drosophila discs-large tumor suppressor protein. The Journal of Cell Biology, 124(6), 949-961. https://doi.org/10.1083/jcb.124.6.949

    Article  CAS  PubMed  Google Scholar 

  120. Haskins, J., Gu, L., Wittchen, E. S., Hibbard, J., & Stevenson, B. R. (1998). ZO-3, a novel member of the MAGUK protein family found at the tight junction, interacts with ZO-1 and occludin. The Journal of Cell Biology, 141(1), 199-208. https://doi.org/10.1083/jcb.141.1.199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Bauer, H., Zweimueller-Mayer, J., Steinbacher, P., Lametschwandtner, A., & Bauer, H. C. (2010). The dual role of zonula occludens (ZO) proteins. Journal of Biomedicine & Biotechnology, 2010, 402593. https://doi.org/10.1155/2010/402593

    Article  CAS  Google Scholar 

  122. Rodgers, L. S., Beam, M. T., Anderson, J. M., & Fanning, A. S. (2013). Epithelial barrier assembly requires coordinated activity of multiple domains of the tight junction protein ZO-1. Journal of Cell Science, 126(Pt 7), 1565-1575. https://doi.org/10.1242/jcs.113399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Suzuki, T. (2013). Regulation of intestinal epithelial permeability by tight junctions. Cellular and Molecular Life Sciences: CMLS, 70(4), 631-659. https://doi.org/10.1007/s00018-012-1070-x

    Article  CAS  PubMed  Google Scholar 

  124. Umeda, K., Ikenouchi, J., Katahira-Tayama, S., Furuse, K., Sasaki, H., Nakayama, M., Matsui, T., Tsukita, S., Furuse, M., & Tsukita, S. (2006). ZO-1 and ZO-2 independently determine where claudins are polymerized in tight-junction strand formation. Cell, 126(4), 741-754. https://doi.org/10.1016/j.cell.2006.06.043

    Article  CAS  PubMed  Google Scholar 

  125. Capaldo, C. T., Koch, S., Kwon, M., Laur, O., Parkos, C. A., & Nusrat, A. (2011). Tight function zonula occludens-3 regulates cyclin D1-dependent cell proliferation. Molecular Biology of the Cell, 22(10), 1677-1685. https://doi.org/10.1091/mbc.E10-08-0677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Garcia, M. A., Nelson, W. J., & Chavez, N. (2018). Cell-Cell Junctions Organize Structural and Signaling Networks. Cold Spring Harbor Perspectives in Biology, 10(4), a029181. https://doi.org/10.1101/cshperspect.a029181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Das, P., Goswami, P., Das, T. K., Nag, T., Sreenivas, V., Ahuja, V., Panda, S. K., Gupta, S. D., & Makharia, G. K. (2012). Comparative tight junction protein expressions in colonic Crohn’s disease, ulcerative colitis, and tuberculosis: A new perspective. Virchows Archiv: An International Journal of Pathology, 460(3), 261-270. https://doi.org/10.1007/s00428-012-1195-1

    Article  CAS  Google Scholar 

  128. Poritz, L. S., Garver, K. I., Green, C., Fitzpatrick, L., Ruggiero, F., & Koltun, W. A. (2007). Loss of the tight junction protein ZO-1 in dextran sulfate sodium induced colitis. The Journal of Surgical Research, 140(1), 12-19. https://doi.org/10.1016/j.jss.2006.07.050

    Article  CAS  PubMed  Google Scholar 

  129. Han, X., Ren, X., Jurickova, I., Groschwitz, K., Pasternak, B. A., Xu, H., Wilson, T. A., Hogan, S. P., & Denson, L. A. (2009). Regulation of intestinal barrier function by signal transducer and activator of transcription 5b. Gut, 58(1), 49-58. https://doi.org/10.1136/gut.2007.145094

    Article  CAS  PubMed  Google Scholar 

  130. Landy, J., Ronde, E., English, N., Clark, S. K., Hart, A. L., Knight, S. C., Ciclitira, P. J., & Al-Hassi, H. O. (2016). Tight junctions in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer. World Journal of Gastroenterology, 22(11), 3117-3126. https://doi.org/10.3748/wjg.v22.i11.3117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Prot-Bertoye, C., & Houillier, P. (2020). Claudins in Renal Physiology and Pathology. Genes, 11(3), E290. https://doi.org/10.3390/genes11030290

    Article  CAS  PubMed  Google Scholar 

  132. Kachar, B., & Reese, T. S. (1982). Evidence for the lipidic nature of tight junction strands. Nature, 296(5856), 464-466. https://doi.org/10.1038/296464a0

    Article  CAS  PubMed  Google Scholar 

  133. Nusrat, A., Parkos, C. A., Verkade, P., Foley, C. S., Liang, T. W., Innis-Whitehouse, W., Eastburn, K. K., & Madara, J. L. (2000). Tight junctions are membrane microdomains. Journal of Cell Science, 113 ( Pt 10), 1771-1781.

    Article  CAS  Google Scholar 

  134. Pinto da Silva, P., & Kachar, B. (1982). On tight-junction structure. Cell, 28(3), 441-450. https://doi.org/10.1016/0092-8674(82)90198-2

    Article  CAS  PubMed  Google Scholar 

  135. Dragsten, P. R., Blumenthal, R., & Handler, J. S. (1981). Membrane asymmetry in epithelia: Is the tight junction a barrier to diffusion in the plasma membrane? Nature, 294(5843), 718-722. https://doi.org/10.1038/294718a0

    Article  CAS  PubMed  Google Scholar 

  136. van Meer, G., & Simons, K. (1986). The function of tight junctions in maintaining differences in lipid composition between the apical and the basolateral cell surface domains of MDCK cells. The EMBO Journal, 5(7), 1455-1464.

    Article  Google Scholar 

  137. Cao, X., Surma, M. A., & Simons, K. (2012). Polarized sorting and trafficking in epithelial cells. Cell Research, 22(5), 793-805. https://doi.org/10.1038/cr.2012.64

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Seo, K., Seo, J., Yeun, J., Choi, H., Kim, Y.-I., & Chang, S.-Y. (2021). The role of mucosal barriers in human gut health. Archives of Pharmacal Research, 44(4), 325-341. https://doi.org/10.1007/s12272-021-01327-5

    Article  CAS  PubMed  Google Scholar 

  139. Camilleri, M. (2019). Leaky gut: Mechanisms, measurement and clinical implications in humans. Gut, 68(8), 1516-1526. https://doi.org/10.1136/gutjnl-2019-318427

    Article  CAS  PubMed  Google Scholar 

  140. Muehler, A., Slizgi, J. R., Kohlhof, H., Groeppel, M., Peelen, E., & Vitt, D. (2020). Clinical relevance of intestinal barrier dysfunction in common gastrointestinal diseases. World Journal of Gastrointestinal Pathophysiology, 11(6), 114-130. https://doi.org/10.4291/wjgp.v11.i6.114

    Article  PubMed  PubMed Central  Google Scholar 

  141. Piche, T. (2014). Tight junctions and IBS--the link between epithelial permeability, low-grade inflammation, and symptom generation? Neurogastroenterology and Motility: The Official Journal of the European Gastrointestinal Motility Society, 26(3), 296-302. https://doi.org/10.1111/nmo.12315

    Article  CAS  Google Scholar 

  142. Brescia, P., & Rescigno, M. (2021). The gut vascular barrier: A new player in the gut-liver-brain axis. Trends in Molecular Medicine, S1471-4914(21)00154-4. https://doi.org/10.1016/j.molmed.2021.06.007

    Article  CAS  Google Scholar 

  143. Mu, Q., Kirby, J., Reilly, C. M., & Luo, X. M. (2017). Leaky Gut As a Danger Signal for Autoimmune Diseases. Frontiers in Immunology, 8, 598. https://doi.org/10.3389/fimmu.2017.00598

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Mg, L., Porfirio, N., & Asma, N. (2008). Role of the intestinal barrier in inflammatory bowel disease. World Journal of Gastroenterology, 14(3), 401-407. https://doi.org/10.3748/wjg.14.401

    Article  CAS  Google Scholar 

  145. Huang, L., Jiang, Y., Sun, Z., Gao, Z., Wang, J., & Zhang, D. (2018). Autophagy Strengthens Intestinal Mucosal Barrier by Attenuating Oxidative Stress in Severe Acute Pancreatitis. Digestive Diseases and Sciences, 63(4), 910-919. https://doi.org/10.1007/s10620-018-4962-2

    Article  CAS  PubMed  Google Scholar 

  146. Ferdinande, L., Demetter, P., Perez-Novo, C., Waeytens, A., Taildeman, J., Rottiers, I., Rottiers, P., De Vos, M., & Cuvelier, C. A. (2008). Inflamed intestinal mucosa features a specific epithelial expression pattern of indoleamine 2,3-dioxygenase. International Journal of Immunopathology and Pharmacology, 21(2), 289-295. https://doi.org/10.1177/039463200802100205

    Article  CAS  PubMed  Google Scholar 

  147. Chelakkot, C., Ghim, J., & Ryu, S. H. (2018). Mechanisms regulating intestinal barrier integrity and its pathological implications. Experimental & Molecular Medicine, 50(8), 1-9. https://doi.org/10.1038/s12276-018-0126-x

    Article  CAS  Google Scholar 

  148. Ferrucci, L., & Fabbri, E. (2018). Inflammageing: Chronic inflammation in ageing, cardiovascular disease, and frailty. Nature Reviews. Cardiology, 15(9), 505-522. https://doi.org/10.1038/s41569-018-0064-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Franceschi, C., Garagnani, P., Parini, P., Giuliani, C., & Santoro, A. (2018). Inflammaging: A new immune-metabolic viewpoint for age-related diseases. Nature Reviews. Endocrinology, 14(10), 576-590. https://doi.org/10.1038/s41574-018-0059-4

    Article  CAS  PubMed  Google Scholar 

  150. Johnson, A. M., & Loftus, E. V. (2021). Obesity in inflammatory bowel disease: A review of its role in the pathogenesis, natural history, and treatment of IBD. Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association. https://doi.org/10.4103/sjg.sjg_30_21

  151. Zhu, X., Li, B., Lou, P., Dai, T., Chen, Y., Zhuge, A., Yuan, Y., & Li, L. (2021). The Relationship Between the Gut Microbiome and Neurodegenerative Diseases. Neuroscience Bulletin. https://doi.org/10.1007/s12264-021-00730-8

  152. Allaire, J. M., Crowley, S. M., Law, H. T., Chang, S.-Y., Ko, H.-J., & Vallance, B. A. (2018). The Intestinal Epithelium: Central Coordinator of Mucosal Immunity. Trends in Immunology, 39(9), 677-696. https://doi.org/10.1016/j.it.2018.04.002

    Article  CAS  PubMed  Google Scholar 

  153. Biagi, E., Nylund, L., Candela, M., Ostan, R., Bucci, L., Pini, E., Nikkïla, J., Monti, D., Satokari, R., Franceschi, C., Brigidi, P., & De Vos, W. (2010). Through ageing, and beyond: Gut microbiota and inflammatory status in seniors and centenarians. PloS One, 5(5), e10667. https://doi.org/10.1371/journal.pone.0010667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Neurath, M. F. (2014). Cytokines in inflammatory bowel disease. Nature Reviews. Immunology, 14(5), 329-342. https://doi.org/10.1038/nri3661

    Article  CAS  PubMed  Google Scholar 

  155. Berkes, J., Viswanathan, V. K., Savkovic, S. D., & Hecht, G. (2003). Intestinal epithelial responses to enteric pathogens: Effects on the tight junction barrier, ion transport, and inflammation. Gut, 52(3), 439-451. https://doi.org/10.1136/gut.52.3.439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Paradis, T., Bègue, H., Basmaciyan, L., Dalle, F., & Bon, F. (2021). Tight Junctions as a Key for Pathogens Invasion in Intestinal Epithelial Cells. International Journal of Molecular Sciences, 22(5), 2506. https://doi.org/10.3390/ijms22052506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Caron, E., Crepin, V. F., Simpson, N., Knutton, S., Garmendia, J., & Frankel, G. (2006). Subversion of actin dynamics by EPEC and EHEC. Current Opinion in Microbiology, 9(1), 40-45. https://doi.org/10.1016/j.mib.2005.12.008

    Article  CAS  PubMed  Google Scholar 

  158. Knutton, S., Lloyd, D. R., & McNeish, A. S. (1987). Adhesion of enteropathogenic Escherichia coli to human intestinal enterocytes and cultured human intestinal mucosa. Infection and Immunity, 55(1), 69-77. https://doi.org/10.1128/iai.55.1.69-77.1987

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Ottlinger, M. E., & Lin, S. (1988). Clostridium difficile toxin B induces reorganization of actin, vinculin, and talin in cultured cells. Experimental Cell Research, 174(1), 215-229. https://doi.org/10.1016/0014-4827(88)90156-5

    Article  CAS  PubMed  Google Scholar 

  160. Booth, B. A., Boesman-Finkelstein, M., & Finkelstein, R. A. (1984). Vibrio cholerae hemagglutinin/protease nicks cholera enterotoxin. Infection and Immunity, 45(3), 558-560. https://doi.org/10.1128/iai.45.3.558-560.1984

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Moncrief, J. S., Obiso, R., Barroso, L. A., Kling, J. J., Wright, R. L., Van Tassell, R. L., Lyerly, D. M., & Wilkins, T. D. (1995). The enterotoxin of Bacteroides fragilis is a metalloprotease. Infection and Immunity, 63(1), 175-181. https://doi.org/10.1128/iai.63.1.175-181.1995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Myers, L. L., Shoop, D. S., Stackhouse, L. L., Newman, F. S., Flaherty, R. J., Letson, G. W., & Sack, R. B. (1987). Isolation of enterotoxigenic Bacteroides fragilis from humans with diarrhea. Journal of Clinical Microbiology, 25(12), 2330-2333. https://doi.org/10.1128/jcm.25.12.2330-2333.1987

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Freedman, J. C., Shrestha, A., & McClane, B. A. (2016). Clostridium perfringens Enterotoxin: Action, Genetics, and Translational Applications. Toxins, 8(3), E73. https://doi.org/10.3390/toxins8030073

    Article  CAS  PubMed  Google Scholar 

  164. Simonovic, I., Rosenberg, J., Koutsouris, A., & Hecht, G. (2000). Enteropathogenic Escherichia coli dephosphorylates and dissociates occludin from intestinal epithelial tight junctions. Cellular Microbiology, 2(4), 305-315. https://doi.org/10.1046/j.1462-5822.2000.00055.x

    Article  CAS  PubMed  Google Scholar 

  165. Viswanathan, V. K., Koutsouris, A., Lukic, S., Pilkinton, M., Simonovic, I., Simonovic, M., & Hecht, G. (2004). Comparative Analysis of EspF from Enteropathogenic and Enterohemorrhagic Escherichia coli in Alteration of Epithelial Barrier Function. Infection and Immunity, 72(6), 3218-3227. https://doi.org/10.1128/IAI.72.6.3218-3227.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Muza-Moons, M. M., Schneeberger, E. E., & Hecht, G. A. (2004). Enteropathogenic Escherichia coli infection leads to appearance of aberrant tight junctions strands in the lateral membrane of intestinal epithelial cells. Cellular Microbiology, 6(8), 783-793. https://doi.org/10.1111/j.1462-5822.2004.00404.x

    Article  CAS  PubMed  Google Scholar 

  167. Campbell, J. A., Schelling, P., Wetzel, J. D., Johnson, E. M., Forrest, J. C., Wilson, G. A. R., Aurrand-Lions, M., Imhof, B. A., Stehle, T., & Dermody, T. S. (2005). Junctional Adhesion Molecule A Serves as a Receptor for Prototype and Field-Isolate Strains of Mammalian Reovirus. Journal of Virology, 79(13), 7967-7978. https://doi.org/10.1128/JVI.79.13.7967-7978.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Cohen, C. J., Shieh, J. T., Pickles, R. J., Okegawa, T., Hsieh, J. T., & Bergelson, J. M. (2001). The coxsackievirus and adenovirus receptor is a transmembrane component of the tight junction. Proceedings of the National Academy of Sciences of the United States of America, 98(26), 15191-15196. https://doi.org/10.1073/pnas.261452898

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Nava, P., López, S., Arias, C. F., Islas, S., & González-Mariscal, L. (2004). The rotavirus surface protein VP8 modulates the gate and fence function of tight junctions in epithelial cells. Journal of Cell Science, 117(Pt 23), 5509-5519. https://doi.org/10.1242/jcs.01425

    Article  CAS  PubMed  Google Scholar 

  170. Guttman, J. A., & Finlay, B. B. (2009). Tight junctions as targets of infectious agents Biochimica et Biophysica Acta (BBA) - Biomembranes, 1788(4), 832-841. https://doi.org/10.1016/j.bbamem.2008.10.028

    Article  CAS  Google Scholar 

  171. Simonovic, I., Arpin, M., Koutsouris, A., Falk-Krzesinski, H. J., & Hecht, G. (2001). Enteropathogenic Escherichia coli Activates Ezrin, Which Participates in Disruption of Tight Junction Barrier Function. Infection and Immunity, 69(9), 5679-5688. https://doi.org/10.1128/IAI.69.9.5679-5688.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Gasaly, N., Hermoso, M. A., & Gotteland, M. (2021). Butyrate and the Fine-Tuning of Colonic Homeostasis: Implication for Inflammatory Bowel Diseases. International Journal of Molecular Sciences, 22(6), 3061. https://doi.org/10.3390/ijms22063061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Geirnaert, A., Calatayud, M., Grootaert, C., Laukens, D., Devriese, S., Smagghe, G., De Vos, M., Boon, N., & Van de Wiele, T. (2017). Butyrate-producing bacteria supplemented in vitro to Crohn’s disease patient microbiota increased butyrate production and enhanced intestinal epithelial barrier integrity. Scientific Reports, 7(1), 11450. https://doi.org/10.1038/s41598-017-11734-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Kumari, R., Ahuja, V., & Paul, J. (2013). Fluctuations in butyrate-producing bacteria in ulcerative colitis patients of North India. World Journal of Gastroenterology, 19(22), 3404-3414. https://doi.org/10.3748/wjg.v19.i22.3404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Louis, P., Young, P., Holtrop, G., & Flint, H. J. (2010). Diversity of human colonic butyrate-producing bacteria revealed by analysis of the butyryl-CoA:acetate CoA-transferase gene. Environmental Microbiology, 12(2), 304-314. https://doi.org/10.1111/j.1462-2920.2009.02066.x

    Article  CAS  PubMed  Google Scholar 

  176. Machiels, K., Joossens, M., Sabino, J., De Preter, V., Arijs, I., Eeckhaut, V., Ballet, V., Claes, K., Van Immerseel, F., Verbeke, K., Ferrante, M., Verhaegen, J., Rutgeerts, P., & Vermeire, S. (2014). A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut, 63(8), 1275-1283. https://doi.org/10.1136/gutjnl-2013-304833

    Article  CAS  PubMed  Google Scholar 

  177. Van den Abbeele, P., Belzer, C., Goossens, M., Kleerebezem, M., De Vos, W. M., Thas, O., De Weirdt, R., Kerckhof, F.-M., & Van de Wiele, T. (2013). Butyrate-producing Clostridium cluster XIVa species specifically colonize mucins in an in vitro gut model. The ISME Journal, 7(5), 949-961. https://doi.org/10.1038/ismej.2012.158

    Article  CAS  PubMed  Google Scholar 

  178. Wang, R. X., Lee, J. S., Campbell, E. L., & Colgan, S. P. (2020a). Microbiota-derived butyrate dynamically regulates intestinal homeostasis through regulation of actin-associated protein synaptopodin. Proceedings of the National Academy of Sciences of the United States of America, 117(21), 11648-11657. https://doi.org/10.1073/pnas.1917597117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Bach Knudsen, K. E., Lærke, H. N., Hedemann, M. S., Nielsen, T. S., Ingerslev, A. K., Gundelund Nielsen, D. S., Theil, P. K., Purup, S., Hald, S., Schioldan, A. G., Marco, M. L., Gregersen, S., & Hermansen, K. (2018). Impact of Diet-Modulated Butyrate Production on Intestinal Barrier Function and Inflammation. Nutrients, 10(10), 1499. https://doi.org/10.3390/nu10101499

    Article  CAS  PubMed Central  Google Scholar 

  180. Coppola, S., Avagliano, C., Calignano, A., & Berni Canani, R. (2021). The Protective Role of Butyrate against Obesity and Obesity-Related Diseases. Molecules, 26(3), 682. https://doi.org/10.3390/molecules26030682

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. McNabney, S. M., & Henagan, T. M. (2017). Short Chain Fatty Acids in the Colon and Peripheral Tissues: A Focus on Butyrate, Colon Cancer, Obesity and Insulin Resistance. Nutrients, 9(12), 1348. https://doi.org/10.3390/nu9121348

    Article  CAS  PubMed Central  Google Scholar 

  182. Stoeva, M. K., Garcia-So, J., Justice, N., Myers, J., Tyagi, S., Nemchek, M., McMurdie, P. J., Kolterman, O., & Eid, J.. (2021). Butyrate-producing human gut symbiont, Clostridium butyricum, and its role in health and disease. Gut Microbes, 13(1), 1907272. https://doi.org/10.1080/19490976.2021.1907272

    Article  CAS  PubMed Central  Google Scholar 

  183. Dinan, T. G., & Cryan, J. F. (2013). Melancholic microbes: A link between gut microbiota and depression? Neurogastroenterology and Motility: The Official Journal of the European Gastrointestinal Motility Society, 25(9), 713-719. https://doi.org/10.1111/nmo.12198

    Article  CAS  Google Scholar 

  184. Finegold, S. M., Dowd, S. E., Gontcharova, V., Liu, C., Henley, K. E., Wolcott, R. D., Youn, E., Summanen, P. H., Granpeesheh, D., Dixon, D., Liu, M., Molitoris, D. R., & Green, J. A. (2010). Pyrosequencing study of fecal microflora of autistic and control children. Anaerobe, 16(4), 444-453. https://doi.org/10.1016/j.anaerobe.2010.06.008

    Article  CAS  PubMed  Google Scholar 

  185. Larsen, N., Vogensen, F. K., van den Berg, F. W. J., Nielsen, D. S., Andreasen, A. S., Pedersen, B. K., Al-Soud, W. A., Sørensen, S. J., Hansen, L. H., & Jakobsen, M. (2010). Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PloS One, 5(2), e9085. https://doi.org/10.1371/journal.pone.0009085

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Matt, S. M., Allen, J. M., Lawson, M. A., Mailing, L. J., Woods, J. A., & Johnson, R. W. (2018). Butyrate and Dietary Soluble Fiber Improve Neuroinflammation Associated With Aging in Mice. Frontiers in Immunology, 9, 1832. https://doi.org/10.3389/fimmu.2018.01832

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Casén, C., Vebø, H. C., Sekelja, M., Hegge, F. T., Karlsson, M. K., Ciemniejewska, E., Dzankovic, S., Frøyland, C., Nestestog, R., Engstrand, L., Munkholm, P., Nielsen, O. H., Rogler, G., Simrén, M., Öhman, L., Vatn, M. H., & Rudi, K. (2015). Deviations in human gut microbiota: A novel diagnostic test for determining dysbiosis in patients with IBS or IBD. Alimentary Pharmacology & Therapeutics, 42(1), 71-83. https://doi.org/10.1111/apt.13236

    Article  CAS  Google Scholar 

  188. Frank, D. N., St Amand, A. L., Feldman, R. A., Boedeker, E. C., Harpaz, N., & Pace, N. R. (2007). Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proceedings of the National Academy of Sciences of the United States of America, 104(34), 13780-13785. https://doi.org/10.1073/pnas.0706625104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Swidsinski, A., Loening-Baucke, V., Vaneechoutte, M., & Doerffel, Y. (2008). Active Crohn’s disease and ulcerative colitis can be specifically diagnosed and monitored based on the biostructure of the fecal flora. Inflammatory Bowel Diseases, 14(2), 147-161. https://doi.org/10.1002/ibd.20330

    Article  PubMed  Google Scholar 

  190. Teh, J. J., Berendsen, E. M., Hoedt, E. C., Kang, S., Zhang, J., Zhang, F., Liu, Q., Hamilton, A. L., Wilson-O’Brien, A., Ching, J., Sung, J. J. Y., Yu, J., Ng, S. C., Kamm, M. A., & Morrison, M. (2021). Novel strain-level resolution of Crohn’s disease mucosa-associated microbiota via an ex vivo combination of microbe culture and metagenomic sequencing. The ISME Journal. https://doi.org/10.1038/s41396-021-00991-1

  191. Aghapour, M., Raee, P., Moghaddam, S. J., Hiemstra, P. S., & Heijink, I. H. (2018). Airway Epithelial Barrier Dysfunction in Chronic Obstructive Pulmonary Disease: Role of Cigarette Smoke Exposure. American Journal of Respiratory Cell and Molecular Biology, 58(2), 157-169. https://doi.org/10.1165/rcmb.2017-0200TR

    Article  CAS  PubMed  Google Scholar 

  192. Andrews, C., McLean, M. H., & Durum, S. K. (2018). Cytokine Tuning of Intestinal Epithelial Function. Frontiers in Immunology, 9, 1270. https://doi.org/10.3389/fimmu.2018.01270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Andriopoulou, P., Navarro, P., Zanetti, A., Lampugnani, M. G., & Dejana, E. (1999). Histamine induces tyrosine phosphorylation of endothelial cell-to-cell adherens junctions. Arteriosclerosis, Thrombosis, and Vascular Biology, 19(10), 2286-2297. https://doi.org/10.1161/01.atv.19.10.2286

    Article  CAS  PubMed  Google Scholar 

  194. Bayarri, M. A., Milara, J., Estornut, C., & Cortijo, J. (2021). Nitric Oxide System and Bronchial Epithelium: More Than a Barrier. Frontiers in Physiology, 12, 687381. https://doi.org/10.3389/fphys.2021.687381

    Article  PubMed  PubMed Central  Google Scholar 

  195. Bazarganipour, S., Hausmann, J., Oertel, S., El-Hindi, K., Brachtendorf, S., Blumenstein, I., Kubesch, A., Sprinzl, K., Birod, K., Hahnefeld, L., Trautmann, S., Thomas, D., Herrmann, E., Geisslinger, G., Schiffmann, S., & Grösch, S. (2019). The Lipid Status in Patients with Ulcerative Colitis: Sphingolipids are Disease-Dependent Regulated. Journal of Clinical Medicine, 8(7), E971. https://doi.org/10.3390/jcm8070971

    Article  CAS  PubMed  Google Scholar 

  196. Bowie, R. V., Donatello, S., Lyes, C., Owens, M. B., Babina, I. S., Hudson, L., Walsh, S. V., O’Donoghue, D. P., Amu, S., Barry, S. P., Fallon, P. G., & Hopkins, A. M. (2012). Lipid rafts are disrupted in mildly inflamed intestinal microenvironments without overt disruption of the epithelial barrier. American Journal of Physiology. Gastrointestinal and Liver Physiology, 302(8), G781-793. https://doi.org/10.1152/ajpgi.00002.2011

    Article  CAS  PubMed  Google Scholar 

  197. El-Salhy, M., Solomon, T., Hausken, T., Gilja, O. H., & Hatlebakk, J. G. (2017). Gastrointestinal neuroendocrine peptides/amines in inflammatory bowel disease. World Journal of Gastroenterology, 23(28), 5068-5085. https://doi.org/10.3748/wjg.v23.i28.5068

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Kessler, E. C., Wall, S. K., Hernandez, L. L., Gross, J. J., & Bruckmaier, R. M. (2019). Short communication: Mammary gland tight junction permeability after parturition is greater in dairy cows with elevated circulating serotonin concentrations. Journal of Dairy Science, 102(2), 1768-1774. https://doi.org/10.3168/jds.2018-15543

    Article  CAS  PubMed  Google Scholar 

  199. Kulkarni, N., Pathak, M., & Lal, G. (2017). Role of chemokine receptors and intestinal epithelial cells in the mucosal inflammation and tolerance. Journal of Leukocyte Biology, 101(2), 377-394. https://doi.org/10.1189/jlb.1RU0716-327R

    Article  CAS  PubMed  Google Scholar 

  200. Luissint, A.-C., Parkos, C. A., & Nusrat, A. (2016). Inflammation and the Intestinal Barrier: Leukocyte-Epithelial Cell Interactions, Cell Junction Remodeling, and Mucosal Repair. Gastroenterology, 151(4), 616-632. https://doi.org/10.1053/j.gastro.2016.07.008

    Article  CAS  PubMed  Google Scholar 

  201. Massironi, S., Zilli, A., Cavalcoli, F., Conte, D., & Peracchi, M. (2016). Chromogranin A and other enteroendocrine markers in inflammatory bowel disease. Neuropeptides, 58, 127-134. https://doi.org/10.1016/j.npep.2016.01.002

    Article  CAS  PubMed  Google Scholar 

  202. Mourad, F. H., Barada, K. A., & Saade, N. E. (2017). Impairment of Small Intestinal Function in Ulcerative Colitis: Role of Enteric Innervation. Journal of Crohn’s & Colitis, 11(3), 369-377. https://doi.org/10.1093/ecco-jcc/jjw162

    Article  Google Scholar 

  203. Zimmerman, N. P., Vongsa, R. A., Wendt, M. K., & Dwinell, M. B. (2008). Chemokines and chemokine receptors in mucosal homeostasis at the intestinal epithelial barrier in inflammatory bowel disease. Inflammatory Bowel Diseases, 14(7), 1000-1011. https://doi.org/10.1002/ibd.20480

    Article  PubMed  Google Scholar 

  204. Kominsky, D. J., Campbell, E. L., Ehrentraut, S. F., Wilson, K. E., Kelly, C. J., Glover, L. E., Collins, C. B., Bayless, A. J., Saeedi, B., Dobrinskikh, E., Bowers, B. E., MacManus, C. F., Müller, W., Colgan, S. P., & Bruder, D. (2014). IFN-γ-mediated induction of an apical IL-10 receptor on polarized intestinal epithelia. Journal of Immunology (Baltimore, Md.: 1950), 192(3), 1267-1276. https://doi.org/10.4049/jimmunol.1301757

    Article  CAS  Google Scholar 

  205. Lee, J., Gonzales-Navajas, J. M., & Raz, E. (2008). The «polarizing-tolerizing» mechanism of intestinal epithelium: Its relevance to colonic homeostasis. Seminars in Immunopathology, 30(1), 3-9. https://doi.org/10.1007/s00281-007-0099-7

    Article  PubMed  Google Scholar 

  206. Serrano, C., Galán, S., Rubio, J. F., Candelario-Martínez, A., Montes-Gómez, A. E., Chánez-Paredes, S., Cedillo-Barrón, L., Schnoor, M., Meraz-Ríos, M. A., Villegas-Sepúlveda, N., Ortiz-Navarrete, V., & Nava, P. (2019). Compartmentalized Response of IL-6/STAT3 Signaling in the Colonic Mucosa Mediates Colitis Development. Journal of Immunology (Baltimore, Md.: 1950), 202(4), 1239-1249. https://doi.org/10.4049/jimmunol.1801060

    Article  CAS  Google Scholar 

  207. Piedra-Quintero, Z. L., Serrano, C., Villegas-Sepúlveda, N., Maravillas-Montero, J. L., Romero-Ramírez, S., Shibayama, M., Medina-Contreras, O., Nava, P., & Santos-Argumedo, L. (2018). Myosin 1F Regulates M1-Polarization by Stimulating Intercellular Adhesion in Macrophages. Frontiers in Immunology, 9, 3118. https://doi.org/10.3389/fimmu.2018.03118

    Article  CAS  PubMed  Google Scholar 

  208. Suzuki, T., Yoshinaga, N., & Tanabe, S. (2011). Interleukin-6 (IL-6) regulates claudin-2 expression and tight junction permeability in intestinal epithelium. The Journal of Biological Chemistry, 286(36), 31263-31271. https://doi.org/10.1074/jbc.M111.238147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Bertheloot, D., Latz, E., & Franklin, B. S. (2021). Necroptosis, pyroptosis and apoptosis: An intricate game of cell death. Cellular and Molecular Immunology, 18(5), 1106-1121. https://doi.org/10.1038/s41423-020-00630-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  210. Castro-Martinez, F., Candelario-Martinez, A., Encarnacion-Garcia, M. D. R., Piedra-Quintero, Z., Bonilla-Moreno, R., Betanzos, A., Perez-Orozco, R., Hernandez-Cueto, M. de L. A., Muñoz-Medina, J. E., Patiño-Lopez, G., Schnoor, M., Villegas-Sepulveda, N., & Nava, P. (2021). Rictor/Mammalian Target of Rapamycin Complex 2 Signaling Protects Colonocytes from Apoptosis and Prevents Epithelial Barrier Breakdown. The American Journal of Pathology, S0002-9440(21)00259-5. https://doi.org/10.1016/j.ajpath.2021.06.004

    Article  CAS  Google Scholar 

  211. Günther, C., Martini, E., Wittkopf, N., Amann, K., Weigmann, B., Neumann, H., Waldner, M. J., Hedrick, S. M., Tenzer, S., Neurath, M. F., & Becker, C. (2011). Caspase-8 regulates TNF-α-induced epithelial necroptosis and terminal ileitis. Nature, 477(7364), 335-339. https://doi.org/10.1038/nature10400

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  212. Piedra-Quintero, Z. L., Wilson, Z., Nava, P., & Guerau-de-Arellano, M. (2020). CD38: An Immunomodulatory Molecule in Inflammation and Autoimmunity. Frontiers in Immunology, 11, 597959. https://doi.org/10.3389/fimmu.2020.597959

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  213. Tanzer, M. C., Frauenstein, A., Stafford, C. A., Phulphagar, K., Mann, M., & Meissner, F. (2020). Quantitative and Dynamic Catalogs of Proteins Released during Apoptotic and Necroptotic Cell Death. Cell Reports, 30(4), 1260-1270.e5. https://doi.org/10.1016/j.celrep.2019.12.079

    Article  CAS  PubMed  Google Scholar 

  214. Garside, P. (1999). Cytokines in experimental colitis. Clinical and Experimental Immunology, 118(3), 337-339. https://doi.org/10.1046/j.1365-2249.1999.01088.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Bhat, A. A., Uppada, S., Achkar, I. W., Hashem, S., Yadav, S. K., Shanmugakonar, M., Al-Naemi, H. A., Haris, M., & Uddin, S. (2018). Tight Junction Proteins and Signaling Pathways in Cancer and Inflammation: A Functional Crosstalk. Frontiers in Physiology, 9, 1942. https://doi.org/10.3389/fphys.2018.01942

    Article  PubMed  Google Scholar 

  216. Balda, M. S., & Matter, K. (2009). Tight junctions and the regulation of gene expression. Biochimica Et Biophysica Acta, 1788(4), 761-767. https://doi.org/10.1016/j.bbamem.2008.11.024

    Article  CAS  PubMed  Google Scholar 

  217. Mankertz, J., Hillenbrand, B., Tavalali, S., Huber, O., Fromm, M., & Schulzke, J. D. (2004). Functional crosstalk between Wnt signaling and Cdx-related transcriptional activation in the regulation of the claudin-2 promoter activity. Biochemical and Biophysical Research Communications, 314(4), 1001-1007. https://doi.org/10.1016/j.bbrc.2003.12.185

    Article  CAS  PubMed  Google Scholar 

  218. Miwa, N., Furuse, M., Tsukita, S., Niikawa, N., Nakamura, Y., & Furukawa, Y. (2001). Involvement of claudin-1 in the beta-catenin/Tcf signaling pathway and its frequent upregulation in human colorectal cancers. Oncology Research, 12(11-12), 469-476. https://doi.org/10.3727/096504001108747477

    Article  CAS  PubMed  Google Scholar 

  219. Bhat, A. A., Sharma, A., Pope, J., Krishnan, M., Washington, M. K., Singh, A. B., & Dhawan, P. (2012). Caudal homeobox protein Cdx-2 cooperates with Wnt pathway to regulate claudin-1 expression in colon cancer cells. PloS One, 7(6), e37174. https://doi.org/10.1371/journal.pone.0037174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  220. Dahan, S., Rabinowitz, K. M., Martin, A. P., Berin, M. C., Unkeless, J. C., & Mayer, L. (2011). Notch-1 signaling regulates intestinal epithelial barrier function, through interaction with CD4+ T cells, in mice and humans. Gastroenterology, 140(2), 550-559. https://doi.org/10.1053/j.gastro.2010.10.057

    Article  CAS  PubMed  Google Scholar 

  221. Mees, S. T., Mennigen, R., Spieker, T., Rijcken, E., Senninger, N., Haier, J., & Bruewer, M. (2009). Expression of tight and adherens junction proteins in ulcerative colitis associated colorectal carcinoma: Upregulation of claudin-1, claudin-3, claudin-4, and beta-catenin. International Journal of Colorectal Disease, 24(4), 361-368. https://doi.org/10.1007/s00384-009-0653-y

    Article  CAS  PubMed  Google Scholar 

  222. Nilsson, A., Peric, A., Strimfors, M., Goodwin, R. J. A., Hayes, M. A., Andrén, P. E., & Hilgendorf, C. (2017). Mass Spectrometry Imaging proves differential absorption profiles of well-characterised permeability markers along the crypt-villus axis. Scientific Reports, 7(1), 6352. https://doi.org/10.1038/s41598-017-06583-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  223. Pearce, S. C., Al-Jawadi, A., Kishida, K., Yu, S., Hu, M., Fritzky, L. F., Edelblum, K. L., Gao, N., & Ferraris, R. P. (2018). Marked differences in tight junction composition and macromolecular permeability among different intestinal cell types. BMC Biology, 16(1), 19. https://doi.org/10.1186/s12915-018-0481-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  224. Pope, J. L., Ahmad, R., Bhat, A. A., Washington, M. K., Singh, A. B., & Dhawan, P. (2014a). Claudin-1 overexpression in intestinal epithelial cells enhances susceptibility to adenamatous polyposis coli-mediated colon tumorigenesis. Molecular Cancer, 13, 167. https://doi.org/10.1186/1476-4598-13-167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. Pope, J. L., Bhat, A. A., Sharma, A., Ahmad, R., Krishnan, M., Washington, M. K., Beauchamp, R. D., Singh, A. B., & Dhawan, P. (2014b). Claudin-1 regulates intestinal epithelial homeostasis through the modulation of Notch-signalling. Gut, 63(4), 622-634. https://doi.org/10.1136/gutjnl-2012-304241

    Article  CAS  PubMed  Google Scholar 

  226. Huber, P. (2020). Targeting of the apical junctional complex by bacterial pathogens. Biochimica Et Biophysica Acta. Biomembranes, 1862(6), 183237. https://doi.org/10.1016/j.bbamem.2020.183237

    Article  CAS  PubMed  Google Scholar 

  227. Lechuga, S., & Ivanov, A. I. (2021). Actin cytoskeleton dynamics during mucosal inflammation: A view from broken epithelial barriers. Current Opinion in Physiology, 19, 10-16. https://doi.org/10.1016/j.cophys.2020.06.012

    Article  PubMed  Google Scholar 

  228. Rusu, A. D., & Georgiou, M. (2020). The multifarious regulation of the apical junctional complex. Open Biology, 10(2), 190278. https://doi.org/10.1098/rsob.190278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  229. Spadaro, D., Tapia, R., Pulimeno, P., & Citi, S. (2012). The control of gene expression and cell proliferation by the epithelial apical junctional complex. Essays in Biochemistry, 53, 83-93. https://doi.org/10.1042/bse0530083

    Article  CAS  PubMed  Google Scholar 

  230. Tsukita, K., Yano, T., Tamura, A., & Tsukita, S. (2019a). Reciprocal Association between the Apical Junctional Complex and AMPK: A Promising Therapeutic Target for Epithelial/Endothelial Barrier Function? International Journal of Molecular Sciences, 20(23), E6012. https://doi.org/10.3390/ijms20236012

    Article  CAS  PubMed  Google Scholar 

  231. Garber, J. J., Mallick, E. M., Scanlon, K. M., Turner, J. R., Donnenberg, M. S., Leong, J. M., & Snapper, S. B. (2018). Attaching-and-Effacing Pathogens Exploit Junction Regulatory Activities of N-WASP and SNX9 to Disrupt the Intestinal Barrier. Cellular and Molecular Gastroenterology and Hepatology, 5(3), 273-288. https://doi.org/10.1016/j.jcmgh.2017.11.015

    Article  PubMed  Google Scholar 

  232. Citalán-Madrid, A. F., Vargas-Robles, H., García-Ponce, A., Shibayama, M., Betanzos, A., Nava, P., Salinas-Lara, C., Rottner, K., Mennigen, R., & Schnoor, M. (2017). Cortactin deficiency causes increased RhoA/ROCK1-dependent actomyosin contractility, intestinal epithelial barrier dysfunction, and disproportionately severe DSS-induced colitis. Mucosal Immunology, 10(5), 1237-1247. https://doi.org/10.1038/mi.2016.136

    Article  CAS  PubMed  Google Scholar 

  233. Wang, D., Naydenov, N. G., Feygin, A., Baranwal, S., Kuemmerle, J. F., & Ivanov, A. I. (2016). Actin-Depolymerizing Factor and Cofilin-1 Have Unique and Overlapping Functions in Regulating Intestinal Epithelial Junctions and Mucosal Inflammation. The American Journal of Pathology, 186(4), 844-858. https://doi.org/10.1016/j.ajpath.2015.11.023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  234. Naydenov, N. G., Feygin, A., Wang, D., Kuemmerle, J. F., Harris, G., Conti, M. A., Adelstein, R. S., & Ivanov, A. I. (2016). Nonmuscle Myosin IIA Regulates Intestinal Epithelial Barrier in vivo and Plays a Protective Role During Experimental Colitis. Scientific Reports, 6, 24161. https://doi.org/10.1038/srep24161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  235. Hegan, P. S., Chandhoke, S. K., Barone, C., Egan, M., Bähler, M., & Mooseker, M. S. (2016). Mice lacking myosin IXb, an inflammatory bowel disease susceptibility gene, have impaired intestinal barrier function and superficial ulceration in the ileum. Cytoskeleton (Hoboken, N.J.), 73(4), 163-179. https://doi.org/10.1002/cm.21292

    Article  CAS  Google Scholar 

  236. McAlpine, W., Wang, K., Choi, J. H., San Miguel, M., McAlpine, S. G., Russell, J., Ludwig, S., Li, X., Tang, M., Zhan, X., Choi, M., Wang, T., Bu, C. H., Murray, A. R., Moresco, E. M. Y., Turer, E. E., & Beutler, B. (2018). The class I myosin MYO1D binds to lipid and protects against colitis. Disease Models & Mechanisms, 11(9), dmm035923. https://doi.org/10.1242/dmm.035923

    Article  CAS  Google Scholar 

  237. Tyska, M. J., Mackey, A. T., Huang, J.-D., Copeland, N. G., Jenkins, N. A., & Mooseker, M. S. (2005). Myosin-1a is critical for normal brush border structure and composition. Molecular Biology of the Cell, 16(5), 2443-2457. https://doi.org/10.1091/mbc.e04-12-1116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  238. Grover, M., Camilleri, M., Hines, J., Burton, D., Ryks, M., Wadhwa, A., Sundt, W., Dyer, R., & Singh, R. J. (2016). (13) C mannitol as a novel biomarker for measurement of intestinal permeability. Neurogastroenterology and Motility: The Official Journal of the European Gastrointestinal Motility Society, 28(7), 1114-1119. https://doi.org/10.1111/nmo.12802

    Article  CAS  Google Scholar 

  239. Khoshbin, K., Khanna, L., Maselli, D., Atieh, J., Breen-Lyles, M., Arndt, K., Rhoten, D., Dyer, R. B., Singh, R. J., Nayar, S., Bjerkness, S., Harmsen, W. S., Busciglio, I., & Camilleri, M. (2021). Development and Validation of Test for «Leaky Gut» Small Intestinal and Colonic Permeability Using Sugars in Healthy Adults. Gastroenterology, S0016-5085(21)00642-9. https://doi.org/10.1053/j.gastro.2021.04.020

    Article  CAS  Google Scholar 

  240. Gupta, R. B., Harpaz, N., Itzkowitz, S., Hossain, S., Matula, S., Kornbluth, A., Bodian, C., & Ullman, T. (2007). Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: A cohort study. Gastroenterology, 133(4), 1099-1105; quiz 1340-1341. https://doi.org/10.1053/j.gastro.2007.08.001

    Article  PubMed  Google Scholar 

  241. Weber, C. R., Nalle, S. C., Tretiakova, M., Rubin, D. T., & Turner, J. R. (2008). Claudin-1 and claudin-2 expression is elevated in inflammatory bowel disease and may contribute to early neoplastic transformation. Laboratory Investigation; a Journal of Technical Methods and Pathology, 88(10), 1110-1120. https://doi.org/10.1038/labinvest.2008.78

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  242. Trier, J. S., & Rubin, C. E. (1964). Electron microscopy of the gut: a word of caution. Gastroenterology, 47, 313-315.

    Article  CAS  Google Scholar 

  243. Severs, N. J. (2007). Freeze-fracture electron microscopy. Nature Protocols, 2(3), 547-576. https://doi.org/10.1038/nprot.2007.55

    Article  CAS  PubMed  Google Scholar 

  244. Suenaert, P., Bulteel, V., Lemmens, L., Noman, M., Geypens, B., Van Assche, G., Geboes, K., Ceuppens, J. L., & Rutgeerts, P. (2002). Anti-tumor necrosis factor treatment restores the gut barrier in Crohn’s disease. The American Journal of Gastroenterology, 97(8), 2000-2004. https://doi.org/10.1111/j.1572-0241.2002.05914.x

    Article  CAS  PubMed  Google Scholar 

  245. Schmitz, H., Barmeyer, C., Gitter, A. H., Wullstein, F., Bentzel, C. J., Fromm, M., Riecken, E. O., & Schulzke, J. D. (2000). Epithelial barrier and transport function of the colon in ulcerative colitis. Annals of the New York Academy of Sciences, 915, 312-326. https://doi.org/10.1111/j.1749-6632.2000.tb05259.x

    Article  CAS  PubMed  Google Scholar 

  246. Crespo, M., Vilar, E., Tsai, S.-Y., Chang, K., Amin, S., Srinivasan, T., Zhang, T., Pipalia, N. H., Chen, H. J., Witherspoon, M., Gordillo, M., Xiang, J. Z., Maxfield, F. R., Lipkin, S., Evans, T., & Chen, S. (2017). Colonic organoids derived from human induced pluripotent stem cells for modeling colorectal cancer and drug testing. Nature Medicine, 23(7), 878-884. https://doi.org/10.1038/nm.4355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  247. McCracken, K. W., Howell, J. C., Wells, J. M., & Spence, J. R. (2011). Generating human intestinal tissue from pluripotent stem cells in vitro. Nature Protocols, 6(12), 1920-1928. https://doi.org/10.1038/nprot.2011.410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  248. Spence, J. R., Mayhew, C. N., Rankin, S. A., Kuhar, M. F., Vallance, J. E., Tolle, K., Hoskins, E. E., Kalinichenko, V. V., Wells, S. I., Zorn, A. M., Shroyer, N. F., & Wells, J. M. (2011). Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature, 470(7332), 105-109. https://doi.org/10.1038/nature09691

    Article  CAS  PubMed  Google Scholar 

  249. Sarvestani, S. K., Signs, S., Hu, B., Yeu, Y., Feng, H., Ni, Y., Hill, D. R., Fisher, R. C., Ferrandon, S., DeHaan, R. K., Stiene, J., Cruise, M., Hwang, T. H., Shen, X., Spence, J. R., & Huang, E. H. (2021). Induced organoids derived from patients with ulcerative colitis recapitulate colitic reactivity. Nature Communications, 12(1), 262. https://doi.org/10.1038/s41467-020-20351-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  250. Liu, Y., & Chen, Y.-G. (2018). 2D- and 3D-Based Intestinal Stem Cell Cultures for Personalized Medicine. Cells, 7(12), E225. https://doi.org/10.3390/cells7120225

    Article  CAS  PubMed  Google Scholar 

  251. Roodsant, T., Navis, M., Aknouch, I., Renes, I. B., van Elburg, R. M., Pajkrt, D., Wolthers, K. C., Schultsz, C., van der Ark, K. C. H., Sridhar, A., & Muncan, V. (2020). A Human 2D Primary Organoid-Derived Epithelial Monolayer Model to Study Host-Pathogen Interaction in the Small Intestine. Frontiers in Cellular and Infection Microbiology, 10, 272. https://doi.org/10.3389/fcimb.2020.00272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

We want to extend our gratitude to Dr. Zayda Piedra Quintero for sharing her expertise in the inflammation field and for her critical discussion of the manuscript. The project was supported by the sectoral funding for research and education via the grant for Basic Science from Conacyt (No. A1-S-20887 to PND) and the SEP-Conacyt grant (No.179 to NV/PND). MREG is the recipient of a doctoral fellowship from Conacyt (860508).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Porfirio Nava .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

del Rocio Encarnacion-Garcia, M., Nava, P. (2022). Tight Junctions in the Inflamed Gut. In: González-Mariscal, L. (eds) Tight Junctions. Springer, Cham. https://doi.org/10.1007/978-3-030-97204-2_6

Download citation

Publish with us

Policies and ethics