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Gene Review

CLDN2  -  claudin 2

Homo sapiens

Synonyms: Claudin-2, PSEC0059, SP82, UNQ705/PRO1356
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Disease relevance of CLDN2


High impact information on CLDN2

  • This permeability defect preceded the development of ileal inflammation, was present in the absence of commensal bacteria, and was accompanied by altered ileal mRNA expression of the tight junction proteins claudin-2 and occludin [5].
  • IL-17 induced formation of tight junctions correlated with up-regulation of claudin-1 and claudin-2 gene transcription [6].
  • Inhibition of MEK reduced the activated and basal expression of claudin-2 messenger RNA and protein expression [6].
  • In conclusion, claudin-2 functions as a paracellular channel to Na(+) to increase the cation selectivity of the tight junction; claudin-4 and -7 function either as paracellular barriers to Na(+) or as paracellular channels to Cl(-), depending upon the cellular background, to decrease the cation selectivity of the tight junction [7].
  • On the other hand, LLC-PK1 cells express little endogenous claudin-2 and show anion selectivity [7].

Chemical compound and disease context of CLDN2


Biological context of CLDN2


Anatomical context of CLDN2


Regulatory relationships of CLDN2


Other interactions of CLDN2

  • 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 [12].
  • The functional role of CDX2, HNF-1alpha, and GATA-4 on claudin-2 regulation was also examined by ectopic expression studies in intestinal cell models [12].
  • Immunohistochemical staining of adult skin was positive for occludin in the intercellular space of the granular layer, and for claudin 1 in the inter-cellular space of the spinosum layer and basal layer, but negative for claudin 2 in all skin layers [13].
  • Functional MEK was required for the expression and membrane association of claudin-2 but not claudin-1 in T84 cells [6].
  • Membrane-bound claudin 3 and 4 expression was seen in all cases of Paget's disease, whereas claudin 5 was seen in 50% of cases and claudin 2 was seen in 32% of cases [3].

Analytical, diagnostic and therapeutic context of CLDN2


  1. Claudin-1 and claudin-2 differentiate fetal and embryonal components in human hepatoblastoma. Halász, J., Holczbauer, A., Páska, C., Kovács, M., Benyó, G., Verebély, T., Schaff, Z., Kiss, A. Hum. Pathol. (2006) [Pubmed]
  2. Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease. Zeissig, S., B??rgel, N., G??nzel, D., Richter, J., Mankertz, J., Wahnschaffe, U., Kroesen, A.J., Zeitz, M., Fromm, M., Schulzke, J.D. Gut (2007) [Pubmed]
  3. Claudins 2, 3, 4, and 5 in Paget's disease and breast carcinoma. Soini, Y. Hum. Pathol. (2004) [Pubmed]
  4. Claudins in differential diagnosis between mesothelioma and metastatic adenocarcinoma of the pleura. Soini, Y., Kinnula, V., Kahlos, K., Pääkkö, P. J. Clin. Pathol. (2006) [Pubmed]
  5. The primary defect in experimental ileitis originates from a nonhematopoietic source. Olson, T.S., Reuter, B.K., Scott, K.G., Morris, M.A., Wang, X.M., Hancock, L.N., Burcin, T.L., Cohn, S.M., Ernst, P.B., Cominelli, F., Meddings, J.B., Ley, K., Pizarro, T.T. J. Exp. Med. (2006) [Pubmed]
  6. Claudins regulate the intestinal barrier in response to immune mediators. Kinugasa, T., Sakaguchi, T., Gu, X., Reinecker, H.C. Gastroenterology (2000) [Pubmed]
  7. Study of claudin function by RNA interference. Hou, J., Gomes, A.S., Paul, D.L., Goodenough, D.A. J. Biol. Chem. (2006) [Pubmed]
  8. Ligation of highly modified bacteriophage DNA. Cao, X.M., Huang, L.H., Farnet, C.M., Ehrlich, M. Biochim. Biophys. Acta (1983) [Pubmed]
  9. PPARgamma-regulated tight junction development during human urothelial cytodifferentiation. Varley, C.L., Garthwaite, M.A., Cross, W., Hinley, J., Trejdosiewicz, L.K., Southgate, J. J. Cell. Physiol. (2006) [Pubmed]
  10. Interleukin-2 receptor beta subunit-dependent and -independent regulation of intestinal epithelial tight junctions. Nishiyama, R., Sakaguchi, T., Kinugasa, T., Gu, X., MacDermott, R.P., Podolsky, D.K., Reinecker, H.C. J. Biol. Chem. (2001) [Pubmed]
  11. Functional crosstalk between Wnt signaling and Cdx-related transcriptional activation in the regulation of the claudin-2 promoter activity. Mankertz, J., Hillenbrand, B., Tavalali, S., Huber, O., Fromm, M., Schulzke, J.D. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  12. Differential expression of claudin-2 along the human intestine: Implication of GATA-4 in the maintenance of claudin-2 in differentiating cells. Escaffit, F., Boudreau, F., Beaulieu, J.F. J. Cell. Physiol. (2005) [Pubmed]
  13. Tight junction proteins: a novel class of integral membrane proteins. Expression in human epidermis and in HaCaT keratinocytes. Tebbe, B., Mankertz, J., Schwarz, C., Amasheh, S., Fromm, M., Assaf, C., Schultz-Ehrenburg, U., Sánchez Ruderish, H., Schulzke, J.D., Orfanos, C.E. Arch. Dermatol. Res. (2002) [Pubmed]
  14. Claudin 1 differentiates endometrioid and serous papillary endometrial adenocarcinoma. Sobel, G., N??meth, J., Kiss, A., Lotz, G., Szab??, I., Udvarhelyi, N., Schaff, Z., P??ska, C. Gynecol. Oncol. (2006) [Pubmed]
  15. Transepithelial Leak in Barrett's Esophagus. Mullin, J.M., Valenzano, M.C., Trembeth, S., Allegretti, P.D., Verrecchio, J.J., Schmidt, J.D., Jain, V., Meddings, J.B., Mercogliano, G., Thornton, J.J. Dig. Dis. Sci. (2006) [Pubmed]
  16. Differential expression of claudin-2 in normal human tissues and gastrointestinal carcinomas. Aung, P.P., Mitani, Y., Sanada, Y., Nakayama, H., Matsusaki, K., Yasui, W. Virchows Arch. (2006) [Pubmed]
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