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Gene Review

CLDN5  -  claudin 5

Homo sapiens

Synonyms: AWAL, BEC1, CPETRL1, Claudin-5, TMDVCF, ...
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Disease relevance of CLDN5

  • Three of these 11 genes (NPTX2, SARP2, and CLDN5) were selected for further analysis in a larger panel of specimens, and aberrant methylation of at least one of these three genes was detectable in 100% of 43 primary pancreatic cancers and in 18 of 24 (75%) pancreatic juice samples obtained from patients with pancreatic cancer [1].
  • Quantification performed determining the expression for TJ-molecules displayed diminished expression for CLDN-1 (p<0.01) and CLDN-5 (p<0.01) in patients with chronic venous insufficiency in comparison with healthy controls on mRNA as well as protein level [2].
  • Densitometric evaluation revealed a more significantly elevated expression (p<0.01) for CLDN-1 and CLDN-5 on mRNA and protein level after four weeks of compression therapy in comparison with prior to treatment for the edema as well as the leg ulcer group [2].
  • Because the primary endothelial TJ molecules, including claudin-5, occludin, and JAM-1, are expressed as early as 16 wk in the blood brain barrier and since as they are not decreased in GM vasculature compared with cortex and white matter, they are unlikely to be responsible for GM fragility and vulnerability to hemorrhage in premature infants [3].
  • Claudin 5 was preferentially expressed only in vessels, and occludin staining ranged from negative to weak in ameloblastomas and teeth germs [4].

High impact information on CLDN5


Biological context of CLDN5

  • The transmission disequilibrium test (TDT) showed that of three SNPs, rs10314 in the 3'-untranslated region of the CLDN5 locus was associated with schizophrenia (chi(2) = 4.75, P = 0.029) [8].
  • The upregulation of claudin 5 correlates with permeability changes that occur during the intermediate stage of RPE development [9].
  • The objective of this study was to compare the expression of endothelial TJ molecules, including claudin-5, occludin, and junction adhesion molecules (JAM), among blood vessels of GM, cortex, and white matter for fetuses and premature infants of gestational age 16-40 wk, and to examine their maturational changes with advancing gestational age [3].
  • By contrast, no changes of barrier properties were detected in cells with a high transepithelial resistance (MDCK-C7) after stable transfection with claudin-5 cDNA [10].
  • The conditioning on genotype test, but not on allele test, revealed a strong association for the combination of the CLDN5 gene with the PLA2G4A gene (chi(2) = 10.17, df = 2, P = 0.006) [11].

Anatomical context of CLDN5


Associations of CLDN5 with chemical compounds

  • Resistance measurements and mannitol fluxes after stable transfection with claudin-5 cDNA revealed a marked increase of barrier function in cells of low genuine transepithelial resistance (Caco-2) [10].
  • Interestingly, this relocation was particularly evident with treatments containing I when probing with Claudin-5 and those containing Se for Occludin [13].
  • We report that GLA, I, and Se alone, or in combination are able to strengthen the function of TJs in human endothelial cells, by way of regulating the distribution of Claudin-5, Occludin, and ZO-1 [13].
  • Synergistic regulation of endothelial tight junctions by antioxidant (Se) and polyunsaturated lipid (GLA) via Claudin-5 modulation [13].

Other interactions of CLDN5


Analytical, diagnostic and therapeutic context of CLDN5




  1. Discovery of novel targets for aberrant methylation in pancreatic carcinoma using high-throughput microarrays. Sato, N., Fukushima, N., Maitra, A., Matsubayashi, H., Yeo, C.J., Cameron, J.L., Hruban, R.H., Goggins, M. Cancer Res. (2003) [Pubmed]
  2. Tight junctions and compression therapy in chronic venous insufficiency. Herouy, Y., Kahle, B., Idzko, M., Eberth, I., Norgauer, J., Pannier, F., Rabe, E., Jünger, M., Bruckner-Tuderman, L. Int. J. Mol. Med. (2006) [Pubmed]
  3. Development of tight junction molecules in blood vessels of germinal matrix, cerebral cortex, and white matter. Ballabh, P., Hu, F., Kumarasiri, M., Braun, A., Nedergaard, M. Pediatr. Res. (2005) [Pubmed]
  4. Claudins 1, 4, 5, 7 and occludin in ameloblastomas and developing human teeth. Bello, I.O., Soini, Y., Slootweg, P.J., Salo, T. J. Oral Pathol. Med. (2007) [Pubmed]
  5. Rho-mediated regulation of tight junctions during monocyte migration across the blood-brain barrier in HIV-1 encephalitis (HIVE). Persidsky, Y., Heilman, D., Haorah, J., Zelivyanskaya, M., Persidsky, R., Weber, G.A., Shimokawa, H., Kaibuchi, K., Ikezu, T. Blood (2006) [Pubmed]
  6. Hypoxia Disrupts the Barrier Function of Neural Blood Vessels through Changes in the Expression of Claudin-5 in Endothelial Cells. Koto, T., Takubo, K., Ishida, S., Shinoda, H., Inoue, M., Tsubota, K., Okada, Y., Ikeda, E. Am. J. Pathol. (2007) [Pubmed]
  7. Paracellular tightness and claudin-5 expression is increased in the BCEC/astrocyte blood-brain barrier model by increasing media buffer capacity during growth. Helms, H.C., Waagepetersen, H.S., Nielsen, C.U., Brodin, B. AAPS. J. (2010) [Pubmed]
  8. The CLDN5 locus may be involved in the vulnerability to schizophrenia. Sun, Z.Y., Wei, J., Xie, L., Shen, Y., Liu, S.Z., Ju, G.Z., Shi, J.P., Yu, Y.Q., Zhang, X., Xu, Q., Hemmings, G.P. Eur. Psychiatry (2004) [Pubmed]
  9. Claudin 5 is transiently expressed during the development of the retinal pigment epithelium. Kojima, S., Rahner, C., Peng, S., Rizzolo, L.J. J. Membr. Biol. (2002) [Pubmed]
  10. Contribution of claudin-5 to barrier properties in tight junctions of epithelial cells. Amasheh, S., Schmidt, T., Mahn, M., Florian, P., Mankertz, J., Tavalali, S., Gitter, A.H., Schulzke, J.D., Fromm, M. Cell Tissue Res. (2005) [Pubmed]
  11. A study of the combined effect of the CLDN5 locus and the genes for the phospholipid metabolism pathway in schizophrenia. Wei, J., Hemmings, G.P. Prostaglandins Leukot. Essent. Fatty Acids (2005) [Pubmed]
  12. The claudin gene family: expression in normal and neoplastic tissues. Hewitt, K.J., Agarwal, R., Morin, P.J. BMC Cancer (2006) [Pubmed]
  13. Synergistic regulation of endothelial tight junctions by antioxidant (Se) and polyunsaturated lipid (GLA) via Claudin-5 modulation. Martin, T.A., Das, T., Mansel, R.E., Jiang, W.G. J. Cell. Biochem. (2006) [Pubmed]
  14. Cell junctional proteins in the human corpus luteum: changes during the normal cycle and after HCG treatment. Groten, T., Fraser, H.M., Duncan, W.C., Konrad, R., Kreienberg, R., Wulff, C. Hum. Reprod. (2006) [Pubmed]
  15. Claudin promotes activation of pro-matrix metalloproteinase-2 mediated by membrane-type matrix metalloproteinases. Miyamori, H., Takino, T., Kobayashi, Y., Tokai, H., Itoh, Y., Seiki, M., Sato, H. J. Biol. Chem. (2001) [Pubmed]
  16. Identification of multiple claudins in the rat epididymis. Gregory, M., Cyr, D.G. Mol. Reprod. Dev. (2006) [Pubmed]
  17. Protein kinase Calpha-RhoA cross-talk in CCL2-induced alterations in brain endothelial permeability. Stamatovic, S.M., Dimitrijevic, O.B., Keep, R.F., Andjelkovic, A.V. J. Biol. Chem. (2006) [Pubmed]
  18. Adrenomedullin improves the blood-brain barrier function through the expression of claudin-5. Honda, M., Nakagawa, S., Hayashi, K., Kitagawa, N., Tsutsumi, K., Nagata, I., Niwa, M. Cell. Mol. Neurobiol. (2006) [Pubmed]
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