Advertisement

Active and passive involvement of claudins in the pathophysiology of intestinal inflammatory diseases

  • Christian Barmeyer
  • Michael Fromm
  • Jörg-Dieter Schulzke
Invited Review

Abstract

Intestinal inflammatory diseases, four of which are discussed here, are associated with alterations of claudins. In ulcerative colitis, diarrhea and antigen entry into the mucosa occurs. Claudin-2 is upregulated but data on other claudins are still limited or vary (e.g., claudin-1 and -4). Apart from that, tight junction changes contribute to diarrhea via a leak flux mechanism, while protection against antigen entry disappears behind epithelial gross lesions (erosions) and apoptotic foci. Crohn’s disease is additionally characterized by a claudin-5 and claudin-8 reduction which plays an active role in antigen uptake already before gross lesions appear. In microscopic colitis (MC), upregulation of claudin-2 expression is weak and a reduction in claudin-4 may be only passively involved, while sodium malabsorption represents the main diarrheal mechanism. However, claudin-5 is removed from MC tight junctions which may be an active trigger for inflammation through antigen uptake along the so-called leaky gut concept. In celiac disease, primary barrier defects are discussed in the context of candidate genes as PARD3 which regulate cell polarity and tight junctions. The loss of claudin-5 allows small antigens to invade, while the reductions in others like claudin-3 are rather passive events. Taken together, the specific role of single tight junction proteins for the onset and perpetuation of inflammation and the recovery from these diseases is far from being fully understood and is clearly dependent on the stage of the disease, the background of the other tight junction components, the transport activity of the mucosa, and the presence of other barrier features like gross lesions, an orchestral interplay which is discussed in this article.

Keywords

Ulcerative colitis Crohn’s disease Microscopic colitis Celiac disease Claudins Barrier defect 

Notes

Acknowledgments

This work is supported by the Deutsche Forschungsgemeinschaft (DFG), grants SCHU 559/11-2 and FR 652/12-1.

References

  1. 1.
    Ahmad R, Chaturvedi R, Olivares-Villagomez D, Habib T, Asim M, Shivesh P, Polk DB, Wilson KT, Washington MK, Van Kaer L, Dhawan P, Singh AB (2014) Targeted colonic claudin-2 expression renders resistance to epithelial injury, induces immune suppression, and protects from colitis. Mucosal immunology 7:1340–1353PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    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:G1054–G1064PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Amasheh M, Fromm A, Krug SM, Amasheh S, Andres S, Zeitz M, Fromm M, Schulzke JD (2010) TNFalpha-induced and berberine-antagonized tight junction barrier impairment via tyrosine kinase, Akt and NFkappaB signaling. J Cell Sci 123:4145–4155PubMedCrossRefGoogle Scholar
  4. 4.
    Amasheh S, Meiri N, Gitter AH, Schoneberg T, Mankertz J, Schulzke JD, Fromm M (2002) Claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells. J Cell Sci 115:4969–4976PubMedCrossRefGoogle Scholar
  5. 5.
    Amasheh S, Milatz S, Krug SM, Bergs M, Amasheh M, Schulzke JD, Fromm M (2009) Na+ absorption defends from paracellular back-leakage by claudin-8 upregulation. Biochem Biophys Res Commun 378:45–50PubMedCrossRefGoogle Scholar
  6. 6.
    Amasheh S, Schmidt T, Mahn M, Florian P, Mankertz J, Tavalali S, Gitter AH, Schulzke JD, Fromm M (2005) Contribution of claudin-5 to barrier properties in tight junctions of epithelial cells. Cell Tissue Res 321:89–96PubMedCrossRefGoogle Scholar
  7. 7.
    Bagnat M, Cheung ID, Mostov KE, Stainier DY (2007) Genetic control of single lumen formation in the zebrafish gut. Nat Cell Biol 9:954–960PubMedCrossRefGoogle Scholar
  8. 8.
    Barmeyer C, Erko I, Fromm A, Bojarski C, Allers K, Moos V, Zeitz M, Fromm M, Schulzke JD (2012) Ion transport and barrier function are disturbed in microscopic colitis. Ann N Y Acad Sci 1258:143–148PubMedCrossRefGoogle Scholar
  9. 9.
    Barmeyer C, Erko I, Fromm A, Bojarski C, Loddenkemper C, Dames P, Kerick M, Siegmund B, Fromm M, Schweiger MR, Schulzke JD (2016) ENaC dysregulation through activation of MEK1/2 contributes to impaired Na+ absorption in lymphocytic colitis. Inflamm Bowel Dis 22:539–547PubMedCrossRefGoogle Scholar
  10. 10.
    Barmeyer C, Schulzke JD, Fromm M (2015) Claudin-related intestinal diseases. Semin Cell Dev Biol 42:30–38PubMedCrossRefGoogle Scholar
  11. 11.
    Barmeyer C, Troeger H, Bojarski C, Siegmund B, Fromm M, Schulzke JD (2014) Lymphocytic colitis-related diarrhea is caused by both, ERK1/2-dependent inhibition of the epithelial sodium channel (ENaC) and a claudin-induced barrier defect. Gastroenterology 146:S-475CrossRefGoogle Scholar
  12. 12.
    Bertiaux-Vandaele N, Youmba SB, Belmonte L, Lecleire S, Antonietti M, Gourcerol G, Leroi AM, Dechelotte P, Menard JF, Ducrotte P, Coeffier M (2011) The expression and the cellular distribution of the tight junction proteins are altered in irritable bowel syndrome patients with differences according to the disease subtype. Am J Gastroenterol 106:2165–2173PubMedCrossRefGoogle Scholar
  13. 13.
    Bodd M, Raki M, Tollefsen S, Fallang LE, Bergseng E, Lundin KE, Sollid LM (2010) HLA-DQ2-restricted gluten-reactive T cells produce IL-21 but not IL-17 or IL-22. Mucosal immunology 3:594–601PubMedCrossRefGoogle Scholar
  14. 14.
    Bruewer M, Luegering A, Kucharzik T, Parkos CA, Madara JL, Hopkins AM, Nusrat A (2003) Proinflammatory cytokines disrupt epithelial barrier function by apoptosis-independent mechanisms. J Immunol 171:6164–6172PubMedCrossRefGoogle Scholar
  15. 15.
    Burgel N, Bojarski C, Mankertz J, Zeitz M, Fromm M, Schulzke JD (2002) Mechanisms of diarrhea in collagenous colitis. Gastroenterology 123:433–443PubMedCrossRefGoogle Scholar
  16. 16.
    Buschmann MM, Shen L, Rajapakse H, Raleigh DR, Wang Y, Wang Y, Lingaraju A, Zha J, Abbott E, McAuley EM, Breskin LA, Wu L, Anderson K, Turner JR, Weber CR (2013) Occludin OCEL-domain interactions are required for maintenance and regulation of the tight junction barrier to macromolecular flux. Mol Biol Cell 24:3056–3068PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Caruso R, Marafini I, Sedda S, Del Vecchio BG, Giuffrida P, MacDonald TT, Corazza GR, Pallone F, Di Sabatino A, Monteleone G (2014) Analysis of the cytokine profile in the duodenal mucosa of refractory coeliac disease patients. Clin Sci 126:451–458PubMedCrossRefGoogle Scholar
  18. 18.
    Coyne CB, Gambling TM, Boucher RC, Carson JL, Johnson LG (2003) Role of claudin interactions in airway tight junctional permeability. American journal of physiology Lung cellular and molecular physiology 285:L1166–L1178PubMedCrossRefGoogle Scholar
  19. 19.
    De Benedetto A, Rafaels NM, McGirt LY, Ivanov AI, Georas SN, Cheadle C, Berger AE, Zhang K, Vidyasagar S, Yoshida T, Boguniewicz M, Hata T, Schneider LC, Hanifin JM, Gallo RL, Novak N, Weidinger S, Beaty TH, Leung DY, Barnes KC, Beck LA (2011) Tight junction defects in patients with atopic dermatitis. The Journal of allergy and clinical immunology 127:773-786–e771-777Google Scholar
  20. 20.
    Del Vecchio G, Tscheik C, Tenz K, Helms HC, Winkler L, Blasig R, Blasig IE (2012) Sodium caprate transiently opens claudin-5-containing barriers at tight junctions of epithelial and endothelial cells. Mol Pharm 9:2523–2533PubMedCrossRefGoogle Scholar
  21. 21.
    Devriese S, Eeckhaut V, Geirnaert A, Van den Bossche L, Hindryckx P, Van de Wiele T, Van Immerseel F, Ducatelle R, De Vos M, and Laukens D (2016). Reduced mucosa-associated Butyricicoccus activity in patients with ulcerative colitis correlates with aberrant claudin-1 expression. J Crohns Colitis. doi: 10.1093/ecco-jcc/jjw142
  22. 22.
    Dong CX, Zhao W, Solomon C, Rowland KJ, Ackerley C, Robine S, Holzenberger M, Gonska T, Brubaker PL (2014) The intestinal epithelial insulin-like growth factor-1 receptor links glucagon-like peptide-2 action to gut barrier function. Endocrinology 155:370–379PubMedCrossRefGoogle Scholar
  23. 23.
    Edelblum KL, Turner JR (2009) The tight junction in inflammatory disease: communication breakdown. Curr Opin Pharmacol 9:715–720PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Epple HJ, Schneider T, Troeger H, Kunkel D, Allers K, Moos V, Amasheh M, Loddenkemper C, Fromm M, Zeitz M, Schulzke JD (2009) Impairment of the intestinal barrier is evident in untreated but absent in suppressively treated HIV-infected patients. Gut 58:220–227PubMedCrossRefGoogle Scholar
  25. 25.
    Fischer A, Gluth M, Pape UF, Wiedenmann B, Theuring F, Baumgart DC (2013) Adalimumab prevents barrier dysfunction and antagonizes distinct effects of TNF-alpha on tight junction proteins and signaling pathways in intestinal epithelial cells. American journal of physiology Gastrointestinal and liver physiology 304:G970–G979PubMedCrossRefGoogle Scholar
  26. 26.
    Fischer A, Gluth M, Weege F, Pape UF, Wiedenmann B, Baumgart DC, Theuring F (2014) Glucocorticoids regulate barrier function and claudin expression in intestinal epithelial cells via MKP-1. American journal of physiology Gastrointestinal and liver physiology 306:G218–G228PubMedCrossRefGoogle Scholar
  27. 27.
    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 54:933–944CrossRefGoogle Scholar
  28. 28.
    Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S (1998) Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol 141:1539–1550PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Furuse M, Furuse K, Sasaki H, Tsukita S (2001) Conversion of zonulae occludentes from tight to leaky strand type by introducing claudin-2 into Madin-Darby canine kidney I cells. J Cell Biol 153:263–272PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Furuse M, Hata M, Furuse K, Yoshida Y, Haratake A, Sugitani Y, Noda T, Kubo A, Tsukita S (2002) Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice. J Cell Biol 156:1099–1111PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Goswami P, Das P, Verma AK, Prakash S, Das TK, Nag TC, Ahuja V, Gupta SD, Makharia GK (2014) Are alterations of tight junctions at molecular and ultrastructural level different in duodenal biopsies of patients with celiac disease and Crohn’s disease? Virchows Archiv : an international journal of pathology 465:521–530CrossRefGoogle Scholar
  32. 32.
    Groschwitz KR, Hogan SP (2009) Intestinal barrier function: molecular regulation and disease pathogenesis. The Journal of allergy and clinical immunology 124:3–20 quiz 21-22PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Grosse B, Cassio D, Yousef N, Bernardo C, Jacquemin E, Gonzales E (2012) Claudin-1 involved in neonatal ichthyosis sclerosing cholangitis syndrome regulates hepatic paracellular permeability. Hepatology 55:1249–1259PubMedCrossRefGoogle Scholar
  34. 34.
    Gunzel D, Yu AS (2013) Claudins and the modulation of tight junction permeability. Physiol Rev 93:525–569PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Hadj-Rabia S, Baala L, Vabres P, Hamel-Teillac D, Jacquemin E, Fabre M, Lyonnet S, De Prost Y, Munnich A, Hadchouel M, Smahi A (2004) Claudin-1 gene mutations in neonatal sclerosing cholangitis associated with ichthyosis: a tight junction disease. Gastroenterology 127:1386–1390PubMedCrossRefGoogle Scholar
  36. 36.
    Hashimoto K, Oshima T, Tomita T, Kim Y, Matsumoto T, Joh T, Miwa H (2008) Oxidative stress induces gastric epithelial permeability through claudin-3. Biochem Biophys Res Commun 376:154–157PubMedCrossRefGoogle Scholar
  37. 37.
    Heller F, Florian P, Bojarski C, Richter J, Christ M, Hillenbrand B, Mankertz J, Gitter AH, Burgel N, Fromm M, Zeitz M, Fuss I, Strober W, Schulzke JD (2005) Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterology 129:550–564PubMedCrossRefGoogle Scholar
  38. 38.
    Hering NA, Andres S, Fromm A, van Tol EA, Amasheh M, Mankertz J, Fromm M, Schulzke JD (2011) Transforming growth factor-beta, a whey protein component, strengthens the intestinal barrier by upregulating claudin-4 in HT-29/B6 cells. J Nutr 141:783–789PubMedCrossRefGoogle Scholar
  39. 39.
    Hering NA, Schulzke JD (2009) Therapeutic options to modulate barrier defects in inflammatory bowel disease. Dig Dis 27:450–454PubMedCrossRefGoogle Scholar
  40. 40.
    Hou J, Gomes AS, Paul DL, Goodenough DA (2006) Study of claudin function by RNA interference. J Biol Chem 281:36117–36123PubMedCrossRefGoogle Scholar
  41. 41.
    Hou J, Renigunta A, Yang J, Waldegger S (2010) Claudin-4 forms paracellular chloride channel in the kidney and requires claudin-8 for tight junction localization. Proc Natl Acad Sci U S A 107:18010–18015PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Ikenouchi J, Furuse M, Furuse K, Sasaki H, Tsukita S, Tsukita S (2005) Tricellulin constitutes a novel barrier at tricellular contacts of epithelial cells. J Cell Biol 171:939–945PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Inai T, Kobayashi J, Shibata Y (1999) Claudin-1 contributes to the epithelial barrier function in MDCK cells. Eur J Cell Biol 78:849–855PubMedCrossRefGoogle Scholar
  44. 44.
    Ishizaki T, Chiba H, Kojima T, Fujibe M, Soma T, Miyajima H, Nagasawa K, Wada I, Sawada N (2003) Cyclic AMP induces phosphorylation of claudin-5 immunoprecipitates and expression of claudin-5 gene in blood-brain-barrier endothelial cells via protein kinase A-dependent and -independent pathways. Exp Cell Res 290:275–288PubMedCrossRefGoogle Scholar
  45. 45.
    Jia W, Lu R, Martin TA, Jiang WG (2014) The role of claudin-5 in blood-brain barrier (BBB) and brain metastases (review). Mol Med Rep 9:779–785PubMedGoogle Scholar
  46. 46.
    Karaki S, Kaji I, Otomo Y, Tazoe H, Kuwahara A (2007) The tight junction component protein, claudin-4, is expressed by enteric neurons in the rat distal colon. Neurosci Lett 428:88–92PubMedCrossRefGoogle Scholar
  47. 47.
    Kinugasa T, Akagi Y, Yoshida T, Ryu Y, Shiratuchi I, Ishibashi N, Shirouzu K (2010) Increased claudin-1 protein expression contributes to tumorigenesis in ulcerative colitis-associated colorectal cancer. Anticancer Res 30:3181–3186PubMedGoogle Scholar
  48. 48.
    Kiuchi-Saishin Y, Gotoh S, Furuse M, Takasuga A, Tano Y, Tsukita S (2002) Differential expression patterns of claudins, tight junction membrane proteins, in mouse nephron segments. Journal of the American Society of Nephrology : JASN 13:875–886PubMedGoogle Scholar
  49. 49.
    Kong WM, Gong J, Dong L, Xu JR (2007) Changes of tight junction claudin-1,-3,-4 protein expression in the intestinal mucosa in patients with irritable bowel syndrome. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 27:1345–1347PubMedGoogle Scholar
  50. 50.
    Krug SM, Schulzke JD, Fromm M (2014) Tight junction, selective permeability, and related diseases. Semin Cell Dev Biol 36:166–176PubMedCrossRefGoogle Scholar
  51. 51.
    Kucharzik T, Walsh SV, Chen J, Parkos CA, Nusrat A (2001) Neutrophil transmigration in inflammatory bowel disease is associated with differential expression of epithelial intercellular junction proteins. Am J Pathol 159:2001–2009PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Li WY, Huey CL, Yu AS (2004) Expression of claudin-7 and -8 along the mouse nephron. American journal of physiology Renal physiology 286:F1063–F1071PubMedCrossRefGoogle Scholar
  53. 53.
    Liu LB, Xue YX, Liu YH, Wang YB (2008) Bradykinin increases blood-tumor barrier permeability by down-regulating the expression levels of ZO-1, occludin, and claudin-5 and rearranging actin cytoskeleton. J Neurosci Res 86:1153–1168PubMedCrossRefGoogle Scholar
  54. 54.
    Matysiak-Budnik T, Candalh C, Dugave C, Namane A, Cellier C, Cerf-Bensussan N, Heyman M (2003) Alterations of the intestinal transport and processing of gliadin peptides in celiac disease. Gastroenterology 125:696–707PubMedCrossRefGoogle Scholar
  55. 55.
    McCarthy KM, Francis SA, McCormack JM, Lai J, Rogers RA, Skare IB, Lynch RD, Schneeberger EE (2000) Inducible expression of claudin-1-myc but not occludin-VSV-G results in aberrant tight junction strand formation in MDCK cells. J Cell Sci 113(Pt 19):3387–3398PubMedGoogle Scholar
  56. 56.
    McLaughlin J, Padfield PJ, Burt JP, O’Neill CA (2004) Ochratoxin A increases permeability through tight junctions by removal of specific claudin isoforms. American journal of physiology Cell physiology 287:C1412–C1417PubMedCrossRefGoogle Scholar
  57. 57.
    Mees ST, 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. Int J Color Dis 24:361–368CrossRefGoogle Scholar
  58. 58.
    Menard S, Lebreton C, Schumann M, Matysiak-Budnik T, Dugave C, Bouhnik Y, Malamut G, Cellier C, Allez M, Crenn P, Schulzke JD, Cerf-Bensussan N, Heyman M (2012) Paracellular versus transcellular intestinal permeability to gliadin peptides in active celiac disease. Am J Pathol 180:608–615PubMedCrossRefGoogle Scholar
  59. 59.
    Michikawa H, Fujita-Yoshigaki J, Sugiya H (2008) Enhancement of barrier function by overexpression of claudin-4 in tight junctions of submandibular gland cells. Cell Tissue Res 334:255–264PubMedCrossRefGoogle Scholar
  60. 60.
    Milatz S, Krug SM, Rosenthal R, Gunzel D, Muller D, Schulzke JD, Amasheh S, Fromm M (2010) Claudin-3 acts as a sealing component of the tight junction for ions of either charge and uncharged solutes. Biochim Biophys Acta 1798:2048–2057PubMedCrossRefGoogle Scholar
  61. 61.
    Mishra A, Prakash S, Sreenivas V, Das TK, Ahuja V, Gupta SD, Makharia GK (2016) Structural and functional changes in the tight junctions of asymptomatic and serology-negative first-degree relatives of patients with celiac disease. J Clin Gastroenterol 50:551–560PubMedCrossRefGoogle Scholar
  62. 62.
    Mitchell LA, Overgaard CE, Ward C, Margulies SS, Koval M (2011) Differential effects of claudin-3 and claudin-4 on alveolar epithelial barrier function. American journal of physiology Lung cellular and molecular physiology 301:L40–L49PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Miyoshi Y, Tanabe S, Suzuki T (2016) Cellular zinc is required for intestinal epithelial barrier maintenance via the regulation of claudin-3 and occludin expression. American journal of physiology Gastrointestinal and liver physiology 311:G105–G116PubMedCrossRefGoogle Scholar
  64. 64.
    Monsuur AJ, de Bakker PI, Alizadeh BZ, Zhernakova A, Bevova MR, Strengman E, Franke L, van’t Slot R, van Belzen MJ, Lavrijsen IC, Diosdado B, Daly MJ, Mulder CJ, Mearin ML, Meijer JW, Meijer GA, van Oort E, Wapenaar MC, Koeleman BP, Wijmenga C (2005) Myosin IXB variant increases the risk of celiac disease and points toward a primary intestinal barrier defect. Nat Genet 37:1341–1344PubMedCrossRefGoogle Scholar
  65. 65.
    Morita K, Furuse M, Fujimoto K, Tsukita S (1999) Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands. Proc Natl Acad Sci U S A 96:511–516PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Morita K, Sasaki H, Furuse M, Tsukita S (1999) Endothelial claudin: claudin-5/TMVCF constitutes tight junction strands in endothelial cells. J Cell Biol 147:185–194PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Nielsen HL, Nielsen H, Ejlertsen T, Engberg J, Gunzel D, Zeitz M, Hering NA, Fromm M, Schulzke JD, Bucker R (2011) Oral and fecal Campylobacter concisus strains perturb barrier function by apoptosis induction in HT-29/B6 intestinal epithelial cells. PLoS One 6:e23858PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Nitta T, Hata M, Gotoh S, Seo Y, Sasaki H, Hashimoto N, Furuse M, Tsukita S (2003) Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice. J Cell Biol 161:653–660PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Ohtsuki S, Sato S, Yamaguchi H, Kamoi M, Asashima T, Terasaki T (2007) Exogenous expression of claudin-5 induces barrier properties in cultured rat brain capillary endothelial cells. J Cell Physiol 210:81–86PubMedCrossRefGoogle Scholar
  70. 70.
    Osada T, Gu YH, Kanazawa M, Tsubota Y, Hawkins BT, Spatz M, Milner R, del Zoppo GJ (2011) Interendothelial claudin-5 expression depends on cerebral endothelial cell-matrix adhesion by beta(1)-integrins. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 31:1972–1985CrossRefGoogle Scholar
  71. 71.
    Oshima T, Miwa H, Joh T (2008) Changes in the expression of claudins in active ulcerative colitis. J Gastroenterol Hepatol 23(Suppl 2):S146–S150PubMedCrossRefGoogle Scholar
  72. 72.
    Piche T, Barbara G, Aubert P, Bruley des Varannes S, Dainese R, Nano JL, Cremon C, Stanghellini V, De Giorgio R, Galmiche JP, Neunlist M (2009) Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators. Gut 58:196–201PubMedCrossRefGoogle Scholar
  73. 73.
    Poritz LS, Harris LR 3rd, Kelly AA, Koltun WA (2011) Increase in the tight junction protein claudin-1 in intestinal inflammation. Dig Dis Sci 56:2802–2809PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Prasad S, Mingrino R, Kaukinen K, Hayes KL, Powell RM, MacDonald TT, Collins JE (2005) Inflammatory processes have differential effects on claudins 2, 3 and 4 in colonic epithelial cells. Laboratory investigation; a journal of technical methods and pathology 85:1139–1162PubMedCrossRefGoogle Scholar
  75. 75.
    Rahner C, Mitic LL, Anderson JM (2001) Heterogeneity in expression and subcellular localization of claudins 2, 3, 4, and 5 in the rat liver, pancreas, and gut. Gastroenterology 120:411–422PubMedCrossRefGoogle Scholar
  76. 76.
    Raleigh DR, Marchiando AM, Zhang Y, Shen L, Sasaki H, Wang Y, Long M, Turner JR (2010) Tight junction-associated MARVEL proteins marveld3, tricellulin, and occludin have distinct but overlapping functions. Mol Biol Cell 21:1200–1213PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Reiter B, Kraft R, Gunzel D, Zeissig S, Schulzke JD, Fromm M, Harteneck C (2006) TRPV4-mediated regulation of epithelial permeability. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20:1802–1812CrossRefGoogle Scholar
  78. 78.
    Rokkam D, Lafemina MJ, Lee JW, Matthay MA, Frank JA (2011) Claudin-4 levels are associated with intact alveolar fluid clearance in human lungs. Am J Pathol 179:1081–1087PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Rosenthal R, Milatz S, Krug SM, Oelrich B, Schulzke JD, Amasheh S, Gunzel D, Fromm M (2010) Claudin-2, a component of the tight junction, forms a paracellular water channel. J Cell Sci 123:1913–1921PubMedCrossRefGoogle Scholar
  80. 80.
    Saeedi BJ, Kao DJ, Kitzenberg DA, Dobrinskikh E, Schwisow KD, Masterson JC, Kendrick AA, Kelly CJ, Bayless AJ, Kominsky DJ, Campbell EL, Kuhn KA, Furuta GT, Colgan SP, Glover LE (2015) HIF-dependent regulation of claudin-1 is central to intestinal epithelial tight junction integrity. Mol Biol Cell 26:2252–2262PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Sandle GI (2005) Pathogenesis of diarrhea in ulcerative colitis: new views on an old problem. J Clin Gastroenterol 39:S49–S52PubMedCrossRefGoogle Scholar
  82. 82.
    Sandle GI, Higgs N, Crowe P, Marsh MN, Venkatesan S, Peters TJ (1990) Cellular basis for defective electrolyte transport in inflamed human colon. Gastroenterology 99:97–105PubMedGoogle Scholar
  83. 83.
    Schmitz H, Barmeyer C, Fromm M, Runkel N, Foss HD, Bentzel CJ, Riecken EO, Schulzke JD (1999) Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis. Gastroenterology 116:301–309PubMedCrossRefGoogle Scholar
  84. 84.
    Schulzke JD, Bentzel CJ, Schulzke I, Riecken EO, Fromm M (1998) Epithelial tight junction structure in the jejunum of children with acute and treated celiac sprue. Pediatr Res 43:435–441PubMedCrossRefGoogle Scholar
  85. 85.
    Schulzke JD, Schulzke I, Fromm M, Riecken EO (1995) Epithelial barrier and ion transport in coeliac sprue: electrical measurements on intestinal aspiration biopsy specimens. Gut 37:777–782PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Schumann M, Gunzel D, Buergel N, Richter JF, Troeger H, May C, Fromm A, Sorgenfrei D, Daum S, Bojarski C, Heyman M, Zeitz M, Fromm M, Schulzke JD (2012) Cell polarity-determining proteins Par-3 and PP-1 are involved in epithelial tight junction defects in coeliac disease. Gut 61:220–228PubMedCrossRefGoogle Scholar
  87. 87.
    Schumann M, Richter JF, Wedell I, Moos V, Zimmermann-Kordmann M, Schneider T, Daum S, Zeitz M, Fromm M, Schulzke JD (2008) Mechanisms of epithelial translocation of the alpha(2)-gliadin-33mer in coeliac sprue. Gut 57:747–754PubMedCrossRefGoogle Scholar
  88. 88.
    Shoar S, Saber AA, Aladdin M, Bashah MM, AlKuwari MJ, Rizwan M, Rosenthal RJ (2016) Bariatric manipulation of gastric arteries: a systematic review on the potential concept for obesity treatment. Int J Surg 36:177–182PubMedCrossRefGoogle Scholar
  89. 89.
    Stamatovic SM, Keep RF, Wang MM, Jankovic I, Andjelkovic AV (2009) Caveolae-mediated internalization of occludin and claudin-5 during CCL2-induced tight junction remodeling in brain endothelial cells. J Biol Chem 284:19053–19066PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Steed E, Rodrigues NT, Balda MS, Matter K (2009) Identification of MarvelD3 as a tight junction-associated transmembrane protein of the occludin family. BMC cell biology 10:95PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Stio M, Retico L, Annese V, Bonanomi AG (2016) Vitamin D regulates the tight-junction protein expression in active ulcerative colitis. Scand J Gastroenterol 51:1193–1199PubMedCrossRefGoogle Scholar
  92. 92.
    Szakal DN, Gyorffy H, Arato A, Cseh A, Molnar K, Papp M, Dezsofi A, Veres G (2010) Mucosal expression of claudins 2, 3 and 4 in proximal and distal part of duodenum in children with coeliac disease. Virchows Archiv : an international journal of pathology 456:245–250CrossRefGoogle Scholar
  93. 93.
    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 140:913–923PubMedCrossRefGoogle Scholar
  94. 94.
    Tamura A, Kitano Y, Hata M, Katsuno T, Moriwaki K, Sasaki H, Hayashi H, Suzuki Y, Noda T, Furuse M, Tsukita S, Tsukita S (2008) Megaintestine in claudin-15-deficient mice. Gastroenterology 134:523–534PubMedCrossRefGoogle Scholar
  95. 95.
    Thuijls G, Derikx JP, de Haan JJ, Grootjans J, de Bruine A, Masclee AA, Heineman E, Buurman WA (2010) Urine-based detection of intestinal tight junction loss. J Clin Gastroenterol 44:e14–e19PubMedCrossRefGoogle Scholar
  96. 96.
    Tian R, Luo Y, Liu Q, Cai M, Li J, Sun W, Wang J, He C, Liu Y, Liu X (2014) The effect of claudin-5 overexpression on the interactions of claudin-1 and -2 and barrier function in retinal cells. Curr Mol Med 14:1226–1237PubMedCrossRefGoogle Scholar
  97. 97.
    van Elburg RM, Uil JJ, Mulder CJ, Heymans HS (1993) Intestinal permeability in patients with coeliac disease and relatives of patients with coeliac disease. Gut 34:354–357PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Van Itallie C, Rahner C, Anderson JM (2001) Regulated expression of claudin-4 decreases paracellular conductance through a selective decrease in sodium permeability. J Clin Invest 107:1319–1327PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Van Itallie CM, Fanning AS, Anderson JM (2003) Reversal of charge selectivity in cation or anion-selective epithelial lines by expression of different claudins. American journal of physiology Renal physiology 285:F1078–F1084PubMedCrossRefGoogle Scholar
  100. 100.
    Wang F, Daugherty B, Keise LL, Wei Z, Foley JP, Savani RC, Koval M (2003) Heterogeneity of claudin expression by alveolar epithelial cells. Am J Respir Cell Mol Biol 29:62–70PubMedCrossRefGoogle Scholar
  101. 101.
    Wapenaar MC, Monsuur AJ, van Bodegraven AA, Weersma RK, Bevova MR, Linskens RK, Howdle P, Holmes G, Mulder CJ, Dijkstra G, van Heel DA, Wijmenga C (2008) Associations with tight junction genes PARD3 and MAGI2 in Dutch patients point to a common barrier defect for coeliac disease and ulcerative colitis. Gut 57:463–467PubMedCrossRefGoogle Scholar
  102. 102.
    Watari A, Hasegawa M, Yagi K, Kondoh M (2016) Checkpoint kinase 1 activation enhances intestinal epithelial barrier function via regulation of claudin-5 expression. PLoS One 11:e0145631PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Watson RE, Poddar R, Walker JM, McGuill I, Hoare LM, Griffiths CE, O’Neill CA (2007) Altered claudin expression is a feature of chronic plaque psoriasis. J Pathol 212:450–458PubMedCrossRefGoogle Scholar
  104. 104.
    Weber CR, Nalle SC, Tretiakova M, Rubin DT, Turner JR (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 88:1110–1120PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Willemsen LE, Hoetjes JP, van Deventer SJ, van Tol EA (2005) Abrogation of IFN-gamma mediated epithelial barrier disruption by serine protease inhibition. Clin Exp Immunol 142:275–284PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Wisner DM, Harris LR 3rd, Green CL, Poritz LS (2008) Opposing regulation of the tight junction protein claudin-2 by interferon-gamma and interleukin-4. J Surg Res 144:1–7PubMedCrossRefGoogle Scholar
  107. 107.
    Wray C, Mao Y, Pan J, Chandrasena A, Piasta F, Frank JA (2009) Claudin-4 augments alveolar epithelial barrier function and is induced in acute lung injury. American journal of physiology Lung cellular and molecular physiology 297:L219–L227PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Yu AS, Enck AH, Lencer WI, Schneeberger EE (2003) Claudin-8 expression in Madin-Darby canine kidney cells augments the paracellular barrier to cation permeation. J Biol Chem 278:17350–17359PubMedCrossRefGoogle Scholar
  109. 109.
    Yuan L, Le Bras A, Sacharidou A, Itagaki K, Zhan Y, Kondo M, Carman CV, Davis GE, Aird WC, Oettgen P (2012) ETS-related gene (ERG) controls endothelial cell permeability via transcriptional regulation of the claudin 5 (CLDN5) gene. J Biol Chem 287:6582–6591PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Zeissig S, Burgel N, Gunzel D, Richter J, Mankertz J, Wahnschaffe U, Kroesen AJ, Zeitz M, Fromm M, Schulzke JD (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 56:61–72PubMedCrossRefGoogle Scholar
  111. 111.
    Zhou W, Cao Q, Peng Y, Zhang QJ, Castrillon DH, DePinho RA, Liu ZP (2009) FoxO4 inhibits NF-kappaB and protects mice against colonic injury and inflammation. Gastroenterology 137:1403–1414PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Institute of Clinical PhysiologyCharité-Universitätsmedizin BerlinBerlinGermany

Personalised recommendations