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.
Similar content being viewed by others
References
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 7:1340–1353
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–G1064
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 123:4145–4155
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 115:4969–4976
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 378:45–50
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 321:89–96
Bagnat M, Cheung ID, Mostov KE, Stainier DY (2007) Genetic control of single lumen formation in the zebrafish gut. Nat Cell Biol 9:954–960
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 1258:143–148
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 22:539–547
Barmeyer C, Schulzke JD, Fromm M (2015) Claudin-related intestinal diseases. Semin Cell Dev Biol 42:30–38
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-475
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 106:2165–2173
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 3:594–601
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 171:6164–6172
Burgel N, Bojarski C, Mankertz J, Zeitz M, Fromm M, Schulzke JD (2002) Mechanisms of diarrhea in collagenous colitis. Gastroenterology 123:433–443
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 24:3056–3068
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 126:451–458
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–L1178
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–e771-777
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 9:2523–2533
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
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 155:370–379
Edelblum KL, Turner JR (2009) The tight junction in inflammatory disease: communication breakdown. Curr Opin Pharmacol 9:715–720
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 58:220–227
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–G979
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–G228
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 54:933–944
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 141:1539–1550
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 153:263–272
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 156:1099–1111
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 465:521–530
Groschwitz KR, Hogan SP (2009) Intestinal barrier function: molecular regulation and disease pathogenesis. The Journal of allergy and clinical immunology 124:3–20 quiz 21-22
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 55:1249–1259
Gunzel D, Yu AS (2013) Claudins and the modulation of tight junction permeability. Physiol Rev 93:525–569
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 127:1386–1390
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 376:154–157
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 129:550–564
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 141:783–789
Hering NA, Schulzke JD (2009) Therapeutic options to modulate barrier defects in inflammatory bowel disease. Dig Dis 27:450–454
Hou J, Gomes AS, Paul DL, Goodenough DA (2006) Study of claudin function by RNA interference. J Biol Chem 281:36117–36123
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 107:18010–18015
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 171:939–945
Inai T, Kobayashi J, Shibata Y (1999) Claudin-1 contributes to the epithelial barrier function in MDCK cells. Eur J Cell Biol 78:849–855
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 290:275–288
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 9:779–785
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 428:88–92
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 30:3181–3186
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 13:875–886
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 27:1345–1347
Krug SM, Schulzke JD, Fromm M (2014) Tight junction, selective permeability, and related diseases. Semin Cell Dev Biol 36:166–176
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 159:2001–2009
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–F1071
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 86:1153–1168
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 125:696–707
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):3387–3398
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–C1417
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 24:361–368
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 180:608–615
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 334:255–264
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 1798:2048–2057
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 50:551–560
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–L49
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–G116
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 37:1341–1344
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 96:511–516
Morita K, Sasaki H, Furuse M, Tsukita S (1999) Endothelial claudin: claudin-5/TMVCF constitutes tight junction strands in endothelial cells. J Cell Biol 147:185–194
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:e23858
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 161:653–660
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 210:81–86
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 31:1972–1985
Oshima T, Miwa H, Joh T (2008) Changes in the expression of claudins in active ulcerative colitis. J Gastroenterol Hepatol 23(Suppl 2):S146–S150
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 58:196–201
Poritz LS, Harris LR 3rd, Kelly AA, Koltun WA (2011) Increase in the tight junction protein claudin-1 in intestinal inflammation. Dig Dis Sci 56:2802–2809
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 85:1139–1162
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 120:411–422
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 21:1200–1213
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 20:1802–1812
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 179:1081–1087
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 123:1913–1921
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 26:2252–2262
Sandle GI (2005) Pathogenesis of diarrhea in ulcerative colitis: new views on an old problem. J Clin Gastroenterol 39:S49–S52
Sandle GI, Higgs N, Crowe P, Marsh MN, Venkatesan S, Peters TJ (1990) Cellular basis for defective electrolyte transport in inflamed human colon. Gastroenterology 99:97–105
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 116:301–309
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 43:435–441
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 37:777–782
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 61:220–228
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 57:747–754
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 36:177–182
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 284:19053–19066
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 10:95
Stio M, Retico L, Annese V, Bonanomi AG (2016) Vitamin D regulates the tight-junction protein expression in active ulcerative colitis. Scand J Gastroenterol 51:1193–1199
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 456:245–250
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 140:913–923
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 134:523–534
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–e19
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 14:1226–1237
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 34:354–357
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 107:1319–1327
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–F1084
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 29:62–70
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 57:463–467
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:e0145631
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 212:450–458
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 88:1110–1120
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 142:275–284
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 144:1–7
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–L227
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 278:17350–17359
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 287:6582–6591
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 56:61–72
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 137:1403–1414
Acknowledgments
This work is supported by the Deutsche Forschungsgemeinschaft (DFG), grants SCHU 559/11-2 and FR 652/12-1.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Barmeyer, C., Fromm, M. & Schulzke, JD. Active and passive involvement of claudins in the pathophysiology of intestinal inflammatory diseases. Pflugers Arch - Eur J Physiol 469, 15–26 (2017). https://doi.org/10.1007/s00424-016-1914-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00424-016-1914-6