CLDN2

Summary

Gene Symbol: CLDN2
Description: claudin 2
Alias: claudin-2, SP82
Species: human
Products:     CLDN2

Top Publications

  1. Oshima T, Miwa H, Joh T. Changes in the expression of claudins in active ulcerative colitis. J Gastroenterol Hepatol. 2008;23 Suppl 2:S146-50 pubmed publisher
    ..Down-regulation of claudin-4 and claudin-7, and up-regulation of claudin-2, might lead to altered TJ structure and be related to the impaired epithelial function in active UC. ..
  2. Tsukita S, Furuse M. Claudin-based barrier in simple and stratified cellular sheets. Curr Opin Cell Biol. 2002;14:531-6 pubmed
    ..Recent advances reveal that claudins - major cell adhesion molecules in tight junctions - are directly involved in this intercellular sealing, not only in simple but also in stratified cellular sheets in vertebrates. ..
  3. Morita K, Furuse M, Fujimoto K, Tsukita S. Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands. Proc Natl Acad Sci U S A. 1999;96:511-6 pubmed
    ..These findings indicated that multiple claudin family members are involved in the formation of TJ strands in various tissues. ..
  4. Aung P, Mitani Y, Sanada Y, Nakayama H, Matsusaki K, Yasui W. Differential expression of claudin-2 in normal human tissues and gastrointestinal carcinomas. Virchows Arch. 2006;448:428-34 pubmed
    ..These results suggest that the expression of claudin-2 may involve organ specificity, and increased expression of claudin-2 may participate in colorectal carcinogenesis. ..
  5. Escaffit F, Boudreau F, Beaulieu J. Differential expression of claudin-2 along the human intestine: Implication of GATA-4 in the maintenance of claudin-2 in differentiating cells. J Cell Physiol. 2005;203:15-26 pubmed
    ..These observations suggest that optimal claudin-2 expression in the gut relies on the presence of GATA-4, suggesting a role for this factor in intestinal regionalization. ..
  6. Mankertz J, Hillenbrand B, Tavalali S, Huber O, Fromm M, Schulzke J. Functional crosstalk between Wnt signaling and Cdx-related transcriptional activation in the regulation of the claudin-2 promoter activity. Biochem Biophys Res Commun. 2004;314:1001-7 pubmed
    ..Moreover, a functional crosstalk between Wnt signaling and transcriptional activation related to caudal-related homeobox (Cdx) proteins could be demonstrated in the regulation of claudin-2 promoter-mediated gene expression. ..
  7. Dhawan P, Ahmad R, Chaturvedi R, Smith J, Midha R, Mittal M, et al. Claudin-2 expression increases tumorigenicity of colon cancer cells: role of epidermal growth factor receptor activation. Oncogene. 2011;30:3234-47 pubmed publisher
    ..Taken together, these results uncover a novel role for claudin-2 in promoting colon cancer, potentially via EGFR transactivation. ..
  8. Sakaguchi T, Gu X, Golden H, Suh E, Rhoads D, Reinecker H. Cloning of the human claudin-2 5'-flanking region revealed a TATA-less promoter with conserved binding sites in mouse and human for caudal-related homeodomain proteins and hepatocyte nuclear factor-1alpha. J Biol Chem. 2002;277:21361-70 pubmed
    ..Tight junction structural components, which determine epithelial polarization and intestinal barrier function, can be regulated by homeodomain proteins that control the differentiation of the intestinal epithelium. ..
  9. Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S. Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol. 1998;141:1539-50 pubmed

More Information

Publications98

  1. Den Beste K, Hoddeson E, Parkos C, Nusrat A, Wise S. Epithelial permeability alterations in an in vitro air-liquid interface model of allergic fungal rhinosinusitis. Int Forum Allergy Rhinol. 2013;3:19-25 pubmed publisher
    ..Given that these cells were not incubated with inflammatory cytokines in vitro, the cultured AFRS epithelial alterations may represent a retained modification in protein expression from the in vivo phenotype. ..
  2. Buchert M, Papin M, Bonnans C, Darido C, Raye W, Garambois V, et al. Symplekin promotes tumorigenicity by up-regulating claudin-2 expression. Proc Natl Acad Sci U S A. 2010;107:2628-33 pubmed publisher
    ..Our results suggest that nuclear overexpression of symplekin promotes tumorigenesis in the human colon and that the regulation of claudin-2 expression is instrumental in this effect. ..
  3. Mankertz J, Amasheh M, Krug S, Fromm A, Amasheh S, Hillenbrand B, et al. TNFalpha up-regulates claudin-2 expression in epithelial HT-29/B6 cells via phosphatidylinositol-3-kinase signaling. Cell Tissue Res. 2009;336:67-77 pubmed publisher
    ..Thus, the up-regulation of claudin-2 by TNFalpha is attributable to the regulation of the expression of the gene, as a result of which epithelial barrier function is disturbed, for example, during chronic intestinal inflammation. ..
  4. Peter Y, Comellas A, Levantini E, Ingenito E, Shapiro S. Epidermal growth factor receptor and claudin-2 participate in A549 permeability and remodeling: implications for non-small cell lung cancer tumor colonization. Mol Carcinog. 2009;48:488-97 pubmed publisher
    ..Understanding the influence of EGF on A549 cell permeability and reorganization will help shed light on NSCLC tumor colonization and contribute to the development of novel anti-cancer treatments. ..
  5. Van Itallie C, Holmes J, Bridges A, Gookin J, Coccaro M, Proctor W, et al. The density of small tight junction pores varies among cell types and is increased by expression of claudin-2. J Cell Sci. 2008;121:298-305 pubmed publisher
    ..Although claudins are likely to be components of the small pores, other factors might regulate pore number. ..
  6. Weber C, Nalle S, Tretiakova M, Rubin D, Turner J. Claudin-1 and claudin-2 expression is elevated in inflammatory bowel disease and may contribute to early neoplastic transformation. Lab Invest. 2008;88:1110-20 pubmed publisher
    ..We speculate that increased claudin-1 and claudin-2 expression may be involved at early stages of transformation in IBD-associated neoplasia. ..
  7. Kinugasa T, Huo Q, Higashi D, Shibaguchi H, Kuroki M, Tanaka T, et al. Selective up-regulation of claudin-1 and claudin-2 in colorectal cancer. Anticancer Res. 2007;27:3729-34 pubmed
    ..Claudin-1 and claudin-2 were found to be overexpressed in CRC tissues. They may be useful as tumor markers and targets for the treatment of colorectal cancer. ..
  8. Lee S, Riley E, Meyer M, Benkusky N, Plum L, DeLuca H, et al. 1,25-Dihydroxyvitamin D3 Controls a Cohort of Vitamin D Receptor Target Genes in the Proximal Intestine That Is Enriched for Calcium-regulating Components. J Biol Chem. 2015;290:18199-215 pubmed publisher
    ..and were composed of genes previously linked to intestinal calcium uptake, including S100g, Trpv6, Atp2b1, and Cldn2 as well as others. An additional distinct network of 56 genes was regulated exclusively by diet...
  9. Luo Y, Jiang Q, Wu J, Qiu J, Zhang W, Mei X, et al. Regulation of migration and invasion by Toll-like receptor-9 signaling network in prostate cancer. Oncotarget. 2015;6:22564-74 pubmed
    ..A few genes, such as odontogenic ameloblast-associated protein (ODAM), claudin 2 (CLDN2), gap junction protein beta 1 (GJB1) and Rho-associated coiled-coil containing protein kinase 1 ..
  10. Takigawa M, Iida M, Nagase S, Suzuki H, Watari A, Tada M, et al. Creation of a Claudin-2 Binder and Its Tight Junction-Modulating Activity in a Human Intestinal Model. J Pharmacol Exp Ther. 2017;363:444-451 pubmed publisher
    ..The transmembrane protein claudin 2 (CLDN2) is a component of epithelial tight junctions (TJs)...
  11. Cherradi S, Martineau P, Gongora C, Del Rio M. Claudin gene expression profiles and clinical value in colorectal tumors classified according to their molecular subtype. Cancer Manag Res. 2019;11:1337-1348 pubmed publisher
    ..Compared with normal mucosa, CLDN1 and CLDN2 were upregulated, whereas CLDN5, 7, 8, and 23 were downregulated in CRC samples...
  12. Shimizu Y, Furuya H, Tamashiro P, Iino K, Chan O, Goodison S, et al. Genetic deletion of Sphingosine Kinase 1 suppresses mouse breast tumor development in a HER2 transgenic model. Carcinogenesis. 2017;: pubmed publisher
    ..Gene expression analysis revealed significant reduction of claudin-2 (CLDN2) expression in tumors from SphK1 deficient mice, suggesting that CLDN2 may mediate SphK1's function...
  13. Walker M, Evock Clover C, Elsasser T, Connor E. Short communication: Glucagon-like peptide-2 and coccidiosis alter tight junction gene expression in the gastrointestinal tract of dairy calves. J Dairy Sci. 2015;98:3432-7 pubmed publisher
    ..The mRNA expression of coxsackie and adenovirus receptor (CXADR), claudins 1, 2, and 4 (CLDN1, CLDN2, and CLDN4), F11 receptor (F11R), junction adhesion molecule 2 (JAM2), occludin (OCLN), and tight junction protein ..
  14. Kim T, Poulin E, Blask E, Bukhalid R, Whitehead R, Franklin J, et al. Myofibroblast keratinocyte growth factor reduces tight junctional integrity and increases claudin-2 levels in polarized Caco-2 cells. Growth Factors. 2012;30:320-32 pubmed
    ..KGF-regulated claudin-2 induction may have implications for inflammatory bowel disease, where both KGF and claudin-2 are upregulated. ..
  15. Yamauchi K, Rai T, Kobayashi K, Sohara E, Suzuki T, Itoh T, et al. Disease-causing mutant WNK4 increases paracellular chloride permeability and phosphorylates claudins. Proc Natl Acad Sci U S A. 2004;101:4690-4 pubmed
    ..The increased paracellular "chloride shunt" caused by the mutant WNK4 could be the pathogenic mechanism of PHAII. ..
  16. Zhang Y, Wu S, Lu R, Zhou D, Zhou J, Carmeliet G, et al. Tight junction CLDN2 gene is a direct target of the vitamin D receptor. Sci Rep. 2015;5:10642 pubmed publisher
    ..knockout (VDR(ΔIEC)) mice, and cultured human intestinal epithelial cells, we demonstrate here that the CLDN2 gene is a direct target of the transcription factor VDR...
  17. Liu H, Wang Y, Sharma A, Mao R, Jiang N, Dun B, et al. Derivatives containing both coumarin and benzimidazole potently induce caspase-dependent apoptosis of cancer cells through inhibition of PI3K-AKT-mTOR signaling. Anticancer Drugs. 2015;26:667-77 pubmed publisher
    ..TSPAN14, TXNIP, and AXL) were significantly upregulated and nine genes (PAGE4, LRP8, SNCAIP, IGFBP5, SLCO2A1, CLDN2, ESRRG, D2HGDH, and PDGFRA) were significantly downregulated...
  18. Wu R, Vazquez Roque M, Carlson P, Burton D, Grover M, Camilleri M, et al. Gluten-induced symptoms in diarrhea-predominant irritable bowel syndrome are associated with increased myosin light chain kinase activity and claudin-15 expression. Lab Invest. 2017;97:14-23 pubmed publisher
    ..The results provide new insight into IBS-D mechanisms and can explain permeability responses to gluten challenge in these patients. ..
  19. Ma F, Ding X, Fan Y, Ying J, Zheng S, Lu N, et al. A CLDN1-negative phenotype predicts poor prognosis in triple-negative breast cancer. PLoS ONE. 2014;9:e112765 pubmed publisher
    ..The membranous expression of CLDN1, CLDN2, CLDN4, and CLDN7 was measured by immunohistochemistry...
  20. Weiss F, Hesselbarth N, Párniczky A, Mosztbacher D, Lämmerhirt F, Ruffert C, et al. Common variants in the CLDN2-MORC4 and PRSS1-PRSS2 loci confer susceptibility to acute pancreatitis. Pancreatology. 2018;: pubmed publisher
    ..Here we analysed whether common variants in the CLDN2-MORC4 and the PRSS1-PRSS2 locus that increase recurrent AP and CP risk associate with AP...
  21. Yu Y, Liu Z, Liu X, Yang L, Geng X, Yang G, et al. Stress-Derived Corticotropin Releasing Factor Breaches Epithelial Endotoxin Tolerance. PLoS ONE. 2013;8:e65760 pubmed publisher
    ..The exposure to CRF also increased the expression of Cldn2 in the epithelial cells, which could be mimicked by over expression of TLR4 in epithelial cells...
  22. Ikari A, Sato T, Watanabe R, Yamazaki Y, Sugatani J. Increase in claudin-2 expression by an EGFR/MEK/ERK/c-Fos pathway in lung adenocarcinoma A549 cells. Biochim Biophys Acta. 2012;1823:1110-8 pubmed publisher
    ..We suggest that a secreted EGF up-regulates the transcriptional activity of claudin-2 mediated by the activation of an EGFR/MEK/ERK/c-Fos pathway in A549 cells. ..
  23. Al Sadi R, Ye D, Boivin M, Guo S, Hashimi M, Ereifej L, et al. Interleukin-6 modulation of intestinal epithelial tight junction permeability is mediated by JNK pathway activation of claudin-2 gene. PLoS ONE. 2014;9:e85345 pubmed publisher
    ..In conclusion, our studies show for the first time that the IL-6 modulation of intestinal TJ permeability was regulated by JNK activation of AP-1 and AP-1 activation of claudin-2 gene. ..
  24. Capaldo C, Farkas A, Hilgarth R, Krug S, Wolf M, Benedik J, et al. Proinflammatory cytokine-induced tight junction remodeling through dynamic self-assembly of claudins. Mol Biol Cell. 2014;25:2710-9 pubmed publisher
    ..These findings establish a model of TJs as self-assembling systems that undergo remodeling in response to proinflammatory cytokines through a mechanism of heterotypic claudin-binding incompatibility. ..
  25. Aghdassi A, Weiss F, Mayerle J, Lerch M, Simon P. Genetic susceptibility factors for alcohol-induced chronic pancreatitis. Pancreatology. 2015;15:S23-31 pubmed publisher
    ..wide search strategies the NAPS study found that polymorphisms in the Trypsin locus (PRSS1 rs10273639), and the Claudin 2 locus (CLDN2-RIPPLY1-MORC4 locus rs7057398 and rs12688220) confer an increased risk of developing alcohol-..
  26. Wisner D, Harris L, Green C, Poritz L. Opposing regulation of the tight junction protein claudin-2 by interferon-gamma and interleukin-4. J Surg Res. 2008;144:1-7 pubmed
    ..Incubation of T84 cells with IFNgamma leads to decreased claudin-2 and increased transepithelial resistance. These cytokines have opposite effects on the expression of claudin-2 and the physiology of the TJ. ..
  27. Tabariès S, Annis M, Hsu B, Tam C, Savage P, Park M, et al. Lyn modulates Claudin-2 expression and is a therapeutic target for breast cancer liver metastasis. Oncotarget. 2015;6:9476-87 pubmed
    ..Our findings may have major clinical implications and advise against the treatment of breast cancer patients with broad-acting SFK inhibitors and support the use of Lyn-specific inhibitors. ..
  28. Nighot P, HU C, Ma T. Autophagy enhances intestinal epithelial tight junction barrier function by targeting claudin-2 protein degradation. J Biol Chem. 2015;290:7234-46 pubmed publisher
    ..Therefore, our data show that autophagy selectively reduces epithelial TJ permeability of ions and small molecules by lysosomal degradation of the TJ protein claudin-2. ..
  29. Moldvay J, Fabian K, Jackel M, Nemeth Z, Bogos K, Furak J, et al. Claudin-1 Protein Expression Is a Good Prognostic Factor in Non-Small Cell Lung Cancer, but only in Squamous Cell Carcinoma Cases. Pathol Oncol Res. 2017;23:151-156 pubmed publisher
    ..Claudin IHC scores of L-ADC differed significantly from ADC (CLDN1: p = 0.009, CLDN2: p = 0.005, CLDN3: p = 0.004, CLDN4: p = 0.001, CLDN7: p < 0...
  30. Colegio O, Van Itallie C, Rahner C, Anderson J. Claudin extracellular domains determine paracellular charge selectivity and resistance but not tight junction fibril architecture. Am J Physiol Cell Physiol. 2003;284:C1346-54 pubmed
    ..These results support a model in which the claudins create paracellular channels and the first extracellular domain is sufficient to determine both paracellular charge selectivity and TER. ..
  31. Lu R, Dalgalan D, Mandell E, Parker S, Ghosh S, Wilson J. PKCι interacts with Rab14 and modulates epithelial barrier function through regulation of claudin-2 levels. Mol Biol Cell. 2015;26:1523-31 pubmed publisher
    ..We showed previously that knockdown of Rab14 results in increased TER and decreased claudin-2. Our results suggest that Rab14 and aPKC interact to regulate trafficking of claudin-2 out of the lysosome-directed pathway. ..
  32. Ferretti E, Tremblay E, Thibault M, Grynspan D, Burghardt K, Bettolli M, et al. The nitric oxide synthase 2 pathway is targeted by both pro- and anti-inflammatory treatments in the immature human intestine. Nitric Oxide. 2017;66:53-61 pubmed publisher
    ..Gene expression of tight junction components such as CLDN1, CLDN2, CLDN7 and OCN and of antioxidant markers such as DUOX2, GPX2, SOD2 were also found to be differentially modulated ..
  33. Hintsala H, Siponen M, Haapasaari K, Karihtala P, Soini Y. Claudins 1, 2, 3, 4, 5 and 7 in solar keratosis and squamocellular carcinoma of the skin. Int J Clin Exp Pathol. 2013;6:2855-63 pubmed
    ..decreased in solar keratosis and skin squamous cell carcinomas compared to normal skin while expression of claudin 2 was increased. With claudins 3 and 5 occasional immunoreactivity was found in squamous cell carcinomas...
  34. Thakur A, Rahman K, Wu J, Bollig A, Biliran H, Lin X, et al. Aberrant expression of X-linked genes RbAp46, Rsk4, and Cldn2 in breast cancer. Mol Cancer Res. 2007;5:171-81 pubmed
    ..of putative tumor suppressor genes Rsk4 and RbAp46 in 47% and 79% of breast carcinoma cases, respectively, whereas Cldn2 was down-regulated in 52% of breast cancer cases compared with normal adjacent tissues...
  35. Bodammer P, Kerkhoff C, Maletzki C, Lamprecht G. Bovine colostrum increases pore-forming claudin-2 protein expression but paradoxically not ion permeability possibly by a change of the intestinal cytokine milieu. PLoS ONE. 2013;8:e64210 pubmed publisher
    ..Thus, modulation of the intestinal transforming growth factor-? expression might have compensated the claudin-2 increase and contributed to the observed barrier strengthening effects of colostrum in vivo and in vitro. ..
  36. Tan S, Duan H, Xun T, Ci W, Qiu J, Yu F, et al. HIV-1 impairs human retinal pigment epithelial barrier function: possible association with the pathogenesis of HIV-associated retinopathy. Lab Invest. 2014;94:777-87 pubmed publisher
    ..Our study highlights the role of HIV-1 in the pathogenesis of HIV/AIDS-related retinopathy and suggests potential therapeutic targets for this ocular complication. ..
  37. Laurila J, Karttunen T, Koivukangas V, Laurila P, Syrjala H, Saarnio J, et al. Tight junction proteins in gallbladder epithelium: different expression in acute acalculous and calculous cholecystitis. J Histochem Cytochem. 2007;55:567-73 pubmed
  38. Nishida M, Yoshida M, Nishiumi S, Furuse M, Azuma T. Claudin-2 regulates colorectal inflammation via myosin light chain kinase-dependent signaling. Dig Dis Sci. 2013;58:1546-59 pubmed publisher
    ..Furthermore, the results of this study indicate that claudin-2 and MLCK are potential therapeutic targets for treatments against intestinal disease. ..
  39. Bai L, Zhang Z, Zhang H, Li X, Yu Q, Lin H, et al. HIV-1 Tat protein alter the tight junction integrity and function of retinal pigment epithelium: an in vitro study. BMC Infect Dis. 2008;8:77 pubmed publisher
    ..The effects of HIV-1 Tat on barrier function of the RPE may be mediated by ERK MAPK and NF-kappaB activation, which may represent potential targets for novel therapeutic approaches for the retinopathy induced by HIV infection. ..
  40. Martínez C, Rodiño Janeiro B, Lobo B, Stanifer M, Klaus B, Granzow M, et al. miR-16 and miR-125b are involved in barrier function dysregulation through the modulation of claudin-2 and cingulin expression in the jejunum in IBS with diarrhoea. Gut. 2017;66:1537-1538 pubmed publisher
    ..identified hsa-miR-125b-5p and hsa-miR-16 as regulating expression of the TJ genes CGN (cingulin) and CLDN2 (claudin-2), respectively...
  41. Norén E, Verma D, Söderkvist P, Weisselberg T, Söderman J, Lotfi K, et al. Single Nucleotide Polymorphisms in MORC4, CD14, and TLR4 Are Related to Outcome of Allogeneic Stem Cell Transplantation. Ann Transplant. 2016;21:56-67 pubmed
    ..between single nucleotide polymorphisms in regions of MORC4, CD14, TLR4, NOD2, SLC22A4, SLC22A5, CARD8, NLRP3, and CLDN2 and the outcomes of patients undergoing allogeneic stem cell transplantation...
  42. Wen M, Zhao H, Liu G, Chen X, Wu B, Tian G, et al. Effect of Zinc Supplementation on Growth Performance, Intestinal Development, and Intestinal Barrier-Related Gene Expression in Pekin Ducks. Biol Trace Elem Res. 2018;183:351-360 pubmed publisher
    ..05), and the messenger RNA (mRNA) levels of leak protein CLDN2 were decreased as the dietary zinc level increased (P < 0.05) at 14 and 35 days of age...
  43. Madsen S, Weber C, Nielsen A, Mohiseni M, Bosssus M, Tipsmark C, et al. Sexual maturation and changes in water and salt transport components in the kidney and intestine of three-spined stickleback (Gasterosteus aculeatus L.). Comp Biochem Physiol A Mol Integr Physiol. 2015;188:107-19 pubmed publisher
    ..nkcc1a, nkcc2, ncc), the cystic fibrosis transmembrane conductance regulator (cftr) and two claudin isoforms (cldn2, cldn15a) were expressed in the intestine and kidney in all groups...
  44. Heiskala M, Peterson P, Yang Y. The roles of claudin superfamily proteins in paracellular transport. Traffic. 2001;2:93-8 pubmed
  45. Giri A, Midha S, Banerjee P, Agrawal A, Mehdi S, Dhingra R, et al. Common Variants in CLDN2 and MORC4 Genes Confer Disease Susceptibility in Patients with Chronic Pancreatitis. PLoS ONE. 2016;11:e0147345 pubmed publisher
    A recent genome-wide association study (GWAS) identified association with variants in X-linked CLDN2 and MORC4, and PRSS1-PRSS2 loci with chronic pancreatitis (CP) in North American patients of European ancestry...
  46. Zhang C, Yan J, Xiao Y, Shen Y, Wang J, Ge W, et al. Inhibition of Autophagic Degradation Process Contributes to Claudin-2 Expression Increase and Epithelial Tight Junction Dysfunction in TNF-α Treated Cell Monolayers. Int J Mol Sci. 2017;18: pubmed publisher
    ..Therefore, we conclude that increase of claudin-2 levels and intestinal epithelial tight junction dysfunction are partly caused by the inhibition of autophagic degradation in TNF-α treated cell monolayers. ..
  47. Denizot J, Sivignon A, Barreau F, Darcha C, Chan H, Stanners C, et al. Adherent-invasive Escherichia coli induce claudin-2 expression and barrier defect in CEABAC10 mice and Crohn's disease patients. Inflamm Bowel Dis. 2012;18:294-304 pubmed publisher
    ..Thus, therapeutic targeting claudin-2 induced by AIEC infection could be a new clinical strategy for preserving intestinal barrier function in CD patients. ..
  48. Song X, Chen H, Wang X, Deng X, Xi Y, He Q, et al. H. pylori-encoded CagA disrupts tight junctions and induces invasiveness of AGS gastric carcinoma cells via Cdx2-dependent targeting of Claudin-2. Cell Immunol. 2013;286:22-30 pubmed publisher
    ..This provides a new mechanism whereby CagA induced dedifferentiation of AGS cells, leading to malignant behavior of biology. ..
  49. Söderman J, Norén E, Christiansson M, Bragde H, Thiébaut R, Hugot J, et al. Analysis of single nucleotide polymorphisms in the region of CLDN2-MORC4 in relation to inflammatory bowel disease. World J Gastroenterol. 2013;19:4935-43 pubmed publisher
    To investigate a possible genetic influence of claudin (CLDN)1, CLDN2 and CLDN4 in the etiology of inflammatory bowel disease...
  50. Li J, Zhuo M, Pei L, Yu A. Conserved aromatic residue confers cation selectivity in claudin-2 and claudin-10b. J Biol Chem. 2013;288:22790-7 pubmed publisher
    ..Our findings provide new insight into how ion selectivity is achieved in the paracellular pore. ..
  51. Krishnan M, McCole D. T cell protein tyrosine phosphatase prevents STAT1 induction of claudin-2 expression in intestinal epithelial cells. Ann N Y Acad Sci. 2017;1405:116-130 pubmed publisher
    ..Moreover, increased claudin-2 in TCPTP-deficient cells requires enhanced STAT1 activation and STAT1 binding to the CLDN2 promoter...
  52. Kojima F, Ishida M, Takikita Suzuki M, Hotta M, Katsura K, Nagata A, et al. Claudin expression profiles in Epstein-Barr virus-associated nasopharyngeal carcinoma. Oncol Rep. 2010;23:927-31 pubmed
    ..Therefore, CPE therapy may be a potential therapeutic target for EBV-associated non-keratinizing NPC, since our results clearly showed claudin-3 and/or -4 expression in all cases studied. ..
  53. Szakál D, Gyorffy H, Arato A, Cseh A, Molnar K, Papp M, et al. Mucosal expression of claudins 2, 3 and 4 in proximal and distal part of duodenum in children with coeliac disease. Virchows Arch. 2010;456:245-50 pubmed publisher
    ..Increased expressions of CLDN 2 and 3 suggest structural changes of tight junction in coeliac disease which may be, at least in part, responsible for increased permeability and proliferation observed in coeliac disease. ..
  54. Rosenthal R, Günzel D, Theune D, Czichos C, Schulzke J, Fromm M. Water channels and barriers formed by claudins. Ann N Y Acad Sci. 2017;1397:100-109 pubmed publisher
    ..The present genetic, molecular, computational, and physiological studies are just now beginning to probe the mechanisms and regulation of paracellular permeation. ..
  55. Amoozadeh Y, Dan Q, Xiao J, Waheed F, Szászi K. Tumor necrosis factor-α induces a biphasic change in claudin-2 expression in tubular epithelial cells: role in barrier functions. Am J Physiol Cell Physiol. 2015;309:C38-50 pubmed publisher
    ..Taken together, the TNF-α-induced changes in claudin-2 levels might contribute to TER changes and could also play a role in newly described functions of claudin-2 such as proliferation regulation. ..
  56. Kniesel U, Wolburg H. Tight junctions of the blood-brain barrier. Cell Mol Neurobiol. 2000;20:57-76 pubmed
    ..4. Recent studies were able to elucidate crucial aspects of the molecular basis of tight junction regulation. An integration of new results into previous morphological work is the central intention of this review. ..
  57. Lim T, Vedula S, Hui S, Kausalya P, Hunziker W, Lim C. Probing effects of pH change on dynamic response of Claudin-2 mediated adhesion using single molecule force spectroscopy. Exp Cell Res. 2008;314:2643-51 pubmed publisher
    ..the kinetic properties of homophilic trans-interactions between full length recombinant GST tagged Claudin-2 (Cldn2) under different pH conditions...
  58. Du W, Xu X, Niu Q, Zhang X, Wei Y, Wang Z, et al. Spi-B-Mediated Silencing of Claudin-2 Promotes Early Dissemination of Lung Cancer Cells from Primary Tumors. Cancer Res. 2017;77:4809-4822 pubmed publisher
    ..and enhanced invasiveness by reconfiguring the chromatin structure of the tight junction gene claudin-2 (CLDN2) and repressing its transcription...
  59. Derikx M, Kovacs P, Scholz M, Masson E, Chen J, Ruffert C, et al. Polymorphisms at PRSS1-PRSS2 and CLDN2-MORC4 loci associate with alcoholic and non-alcoholic chronic pancreatitis in a European replication study. Gut. 2015;64:1426-33 pubmed publisher
    ..pancreatitis (CP) with variants in PRSS1-PRSS2 (rs10273639; near the gene encoding cationic trypsinogen) and CLDN2-MORC4 loci (rs7057398 in RIPPLY1 and rs12688220 in MORC4)...
  60. Tan X, Li D, Wang X, Zeng Y, Yan Y, Yang L. Claudin-2 downregulation by KSHV infection is involved in the regulation of endothelial barrier function. J Cutan Pathol. 2014;41:630-9 pubmed publisher
    ..Decreased claudin-2 enhances endothelial barrier function and may play a role in the prolonged survival of patients with KSHV and HIV co-infection. ..
  61. Fujii N, Matsuo Y, Matsunaga T, Endo S, Sakai H, Yamaguchi M, et al. Hypotonic Stress-induced Down-regulation of Claudin-1 and -2 Mediated by Dephosphorylation and Clathrin-dependent Endocytosis in Renal Tubular Epithelial Cells. J Biol Chem. 2016;291:24787-24799 pubmed
    ..We suggest that hypotonic stress induces dephosphorylation, clathrin-dependent endocytosis, and degradation of claudin-1 and -2 in lysosomes, resulting in disruption of the TJ barrier in renal tubular epithelial cells. ..
  62. Flores Maldonado C, González Robles A, Salazar Villatoro L, Omaña Molina M, Gallardo J, González Lázaro M, et al. Acanthamoeba (T4) trophozoites cross the MDCK epithelium without cell damage but increase paracellular permeability and transepithelial resistance by modifying tight junction composition. Exp Parasitol. 2017;183:69-75 pubmed publisher
    ..and Western blot assays were performed to locate and estimate expression of TJ protein claudins 2 (Cldn2) and 4 (Cldn4). The results show that Acanthamoeba sp...
  63. Van Itallie C, Mitic L, Anderson J. SUMOylation of claudin-2. Ann N Y Acad Sci. 2012;1258:60-4 pubmed publisher
    ..We conclude that the cellular levels of claudin-2 may be modulated by SUMOylation, warranting further investigation of cellular pathways that regulate this modification in vivo. ..
  64. Lin Z, Zhang X, Liu Z, Liu Q, Wang L, Lu Y, et al. The distinct expression patterns of claudin-2, -6, and -11 between human gastric neoplasms and adjacent non-neoplastic tissues. Diagn Pathol. 2013;8:133 pubmed publisher
    ..The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5470513569630744. ..
  65. Smith A, Schacker T, Reilly C, Haase A. A role for syndecan-1 and claudin-2 in microbial translocation during HIV-1 infection. J Acquir Immune Defic Syndr. 2010;55:306-15 pubmed publisher
    ..We thus propose a new mechanism in which claudin-2 and SYN1 work in concert to enhance microbial translocation across the intestinal epithelial barrier to contribute to chronic immune activation and CD4 T-cell depletion. ..
  66. Sonoki H, Sato T, Endo S, Matsunaga T, Yamaguchi M, Yamazaki Y, et al. Quercetin Decreases Claudin-2 Expression Mediated by Up-Regulation of microRNA miR-16 in Lung Adenocarcinoma A549 Cells. Nutrients. 2015;7:4578-92 pubmed publisher
    ..These results suggest that quercetin decreases claudin-2 expression mediated by up-regulation of miR-16 expression and instability of claudin-2 mRNA in lung adenocarcinoma cells. ..
  67. Kim S, Kim G. Roles of claudin-2, ZO-1 and occludin in leaky HK-2 cells. PLoS ONE. 2017;12:e0189221 pubmed publisher
    ..We demonstrated that integration of claudin-2, occludin and ZO-1 is necessary for maintaining the function of the proximal tubular epithelium. ..
  68. Xin S, Huixin C, Benchang S, Aiping B, Jinhui W, Xiaoyan L, et al. Expression of Cdx2 and claudin-2 in the multistage tissue of gastric carcinogenesis. Oncology. 2007;73:357-65 pubmed publisher
    ..112, p < 0.05). Thus, there may be a correlation between the expression of claudin-2 and Cdx2 in stages of dysplasia and cancer. ..
  69. Wang Y, Mumm J, Herbst R, Kolbeck R, Wang Y. IL-22 Increases Permeability of Intestinal Epithelial Tight Junctions by Enhancing Claudin-2 Expression. J Immunol. 2017;199:3316-3325 pubmed publisher
    ..These results provide novel mechanistic insights into the role of IL-22 in the regulation and maintenance of the intestinal epithelial barrier. ..
  70. Zheng L, Kelly C, Battista K, Schaefer R, Lanis J, Alexeev E, et al. Microbial-Derived Butyrate Promotes Epithelial Barrier Function through IL-10 Receptor-Dependent Repression of Claudin-2. J Immunol. 2017;199:2976-2984 pubmed publisher
    ..Our findings provide a novel mechanism by which microbial-derived butyrate promotes barrier through IL-10RA-dependent repression of claudin-2. ..
  71. Kimbung S, Kovács A, Bendahl P, Malmström P, Fernö M, Hatschek T, et al. Claudin-2 is an independent negative prognostic factor in breast cancer and specifically predicts early liver recurrences. Mol Oncol. 2014;8:119-28 pubmed publisher
    ..Two-sided statistical tests were used. CLDN2 was significantly up-regulated (P < 0.001) in liver metastases compared to other metastatic sites...
  72. Hichino A, Okamoto M, Taga S, Akizuki R, Endo S, Matsunaga T, et al. Down-regulation of Claudin-2 Expression and Proliferation by Epigenetic Inhibitors in Human Lung Adenocarcinoma A549 Cells. J Biol Chem. 2017;292:2411-2421 pubmed publisher
    ..We suggest that epigenetic inhibitors suppress the abnormal proliferation of lung adenocarcinoma cells highly expressing claudin-2. ..
  73. Abu Farsakh S, Wu T, LaLonde A, Sun J, Zhou Z. High expression of Claudin-2 in esophageal carcinoma and precancerous lesions is significantly associated with the bile salt receptors VDR and TGR5. BMC Gastroenterol. 2017;17:33 pubmed publisher
    ..Our studies identify a novel role of a tight junction protein in the development and progression of esophageal mucosal metaplasia, dysplasia and carcinoma. ..
  74. Itoh M, Furuse M, Morita K, Kubota K, Saitou M, Tsukita S. Direct binding of three tight junction-associated MAGUKs, ZO-1, ZO-2, and ZO-3, with the COOH termini of claudins. J Cell Biol. 1999;147:1351-63 pubmed
    ..In good agreement, PDZ1 and PDZ2 domains of ZO-1/ZO-2/ZO-3 were also recruited to claudin-based TJs, when introduced into cultured epithelial cells. The possible molecular architecture of TJ plaque structures is discussed. ..
  75. Weber C, Liang G, Wang Y, Das S, Shen L, Yu A, et al. Claudin-2-dependent paracellular channels are dynamically gated. elife. 2015;4:e09906 pubmed publisher
    ..We conclude that claudin-2 forms gated paracellular channels and speculate that modulation of tight junction channel gating kinetics may be an unappreciated mechanism of barrier regulation. ..
  76. Tsukita S, Furuse M, Itoh M. Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol. 2001;2:285-93 pubmed
    ..New insights into the molecular architecture of tight junctions allow us to now discuss the structure and functions of this unique cell-cell adhesion apparatus in molecular terms. ..
  77. Tian R, Luo Y, Liu Q, Cai M, Li J, Sun W, et al. The effect of claudin-5 overexpression on the interactions of claudin-1 and -2 and barrier function in retinal cells. Curr Mol Med. 2014;14:1226-37 pubmed
    ..Claudin elements and their interactions can be modulated and that such dynamic properties are important for the functions of TJs, ranging from the regulation of retinal barrier integrity to junction-associated signaling mechanisms. ..
  78. Wilmes A, Aschauer L, Limonciel A, Pfaller W, Jennings P. Evidence for a role of claudin 2 as a proximal tubular stress responsive paracellular water channel. Toxicol Appl Pharmacol. 2014;279:163-72 pubmed publisher
    ..Knock down of claudin 2 by shRNA had no discernable effect on TEER or dome formation but severely attenuated apical to basolateral water ..
  79. Whitcomb D, Larusch J, Krasinskas A, Klei L, Smith J, Brand R, et al. Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis. Nat Genet. 2012;44:1349-54 pubmed publisher
    ..at genome-wide significance identified and replicated at PRSS1-PRSS2 (P < 1 × 10(-12)) and X-linked CLDN2 (P < 1 × 10(-21)) through a two-stage genome-wide study (stage 1: 676 cases and 4,507 controls; stage 2: 910 ..
  80. Moldvay J, Jackel M, Páska C, Soltesz I, Schaff Z, Kiss A. Distinct claudin expression profile in histologic subtypes of lung cancer. Lung Cancer. 2007;57:159-67 pubmed
  81. Song X, Li X, Tang Y, Chen H, Wong B, Wang J, et al. Expression of claudin-2 in the multistage process of gastric carcinogenesis. Histol Histopathol. 2008;23:673-82 pubmed publisher
    ..001). This suggests that claudin-2 protein overexpression may be closely correlated to gastric carcinogenesis. ..
  82. Ikari A, Watanabe R, Sato T, Taga S, Shimobaba S, Yamaguchi M, et al. Nuclear distribution of claudin-2 increases cell proliferation in human lung adenocarcinoma cells. Biochim Biophys Acta. 2014;1843:2079-88 pubmed publisher
    ..We suggest that nuclear distribution of claudin-2 is up-regulated by dephosphorylation and claudin-2 serves to retain ZONAB and cyclin D1 in the nucleus, resulting in the enhancement of cell proliferation in lung adenocarcinoma cells. ..
  83. Tabaries S, Dong Z, Annis M, Omeroglu A, Pepin F, Ouellet V, et al. Claudin-2 is selectively enriched in and promotes the formation of breast cancer liver metastases through engagement of integrin complexes. Oncogene. 2011;30:1318-28 pubmed publisher
    ..Together, these results uncover novel roles for claudin-2 in promoting breast cancer adhesion to the ECM and define its importance during breast cancer metastasis to the liver. ..
  84. Ishida M, Kushima R, Okabe H. Claudin expression in rectal well-differentiated endocrine neoplasms (carcinoid tumors). Oncol Rep. 2009;21:113-7 pubmed
  85. Fujita H, Sugimoto K, Inatomi S, Maeda T, Osanai M, Uchiyama Y, et al. Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes. Mol Biol Cell. 2008;19:1912-21 pubmed publisher
    ..These findings strongly suggest that claudin-2- and/or claudin-12-based tight junctions form paracellular Ca(2+) channels in intestinal epithelia, and they highlight a novel mechanism behind vitamin D-dependent calcium homeostasis. ..
  86. Nomme J, Antanasijevic A, Caffrey M, Van Itallie C, Anderson J, Fanning A, et al. Structural Basis of a Key Factor Regulating the Affinity between the Zonula Occludens First PDZ Domain and Claudins. J Biol Chem. 2015;290:16595-606 pubmed publisher
    ..Plasticity has been recognized as a critical property of TJs that allow cell remodeling and migration. Our work provides a molecular framework for how TJ plasticity may be regulated. ..
  87. Gonzalez Mariscal L, Betanzos A, Nava P, Jaramillo B. Tight junction proteins. Prog Biophys Mol Biol. 2003;81:1-44 pubmed
  88. Mullin J, Valenzano M, Trembeth S, Allegretti P, Verrecchio J, Schmidt J, et al. Transepithelial leak in Barrett's esophagus. Dig Dis Sci. 2006;51:2326-36 pubmed