Disease relevance of Cldn5

• These data demonstrate that claudin-5 is specifically altered in dko hearts, suggesting that alterations of the lateral membranes of cardiomyocytes, rather than intercalated discs, are associated with cardiomyopathy in the dko mouse [1].
• Among these, claudin-5 (also called transmembrane protein deleted in velo-cardio-facial syndrome [TMVCF]) was expressed ubiquitously, even in organs lacking epithelial tissues, suggesting the possible involvement of this claudin species in endothelial TJs [2].
• Helicobacter pylori activates myosin light-chain kinase to disrupt claudin-4 and claudin-5 and increase epithelial permeability [3].
• These in vitro and in vivo data indicate that claudin-5 is a target molecule of hypoxia leading to the disruption of the barrier function of neural vasculature [4].
• When injected subcutaneously in nude mice, MAECs induced the appearance of slow-growing vascular lesions reminiscent of epithelioid hemangioendothelioma, whereas MBEC xenografts grew rapidly, showing Kaposi's sarcoma-like morphological features [5].

High impact information on Cldn5

• Moreover, SB-431542 up-regulated the expression of claudin-5, an endothelial specific component of tight junctions [6].
• In contrast, in the kidney, the claudin-5/TMVCF signal was restricted to endothelial cells of arteries, but was undetectable in those of veins and capillaries [2].
• In addition, in all other tissues we examined, claudin-5/TMVCF was specifically detected in endothelial cells of some segments of blood vessels, but not in epithelial cells [2].
• Furthermore, when claudin-5/TMVCF cDNA was introduced into mouse L fibroblasts, TJ strands were reconstituted that resembled those in endothelial cells in vivo, i.e., the extracellular face-associated TJs [2].
• In particular, the conserved cysteines were crucial: mutation of either cysteine abolishted the ability of claudin-5 to increase transepithelial resistance, and mutation of Cys(64) strikingly increased the paracellular flux of monosaccharides [7].

Chemical compound and disease context of Cldn5

• Luminal to abluminal PMT of 131I-HIV-1 was 4.65 times greater than that of the much smaller 131I-BSA, showing that the MBEC monolayer is more permeable to HIV-1 than to BSA [8].

Biological context of Cldn5

• Transfection of TR-BBB cells with the claudin-5 gene afforded TR-BBB/CLD5 cells, which showed no change in expression of claudin-12 or ZO-1, while the expressed claudin-5 was detected at the cell-cell boundaries [9].
• In conclusion, disruptions of the tight junctions observed in this study implicate host cell signaling pathways, including the phosphorylation of myosin light chain and the regulation of tight-junctional proteins claudin-4 and claudin-5, in the pathogenesis of H. pylori infection [3].
• The movement of claudin-5 from the cytoplasm to the plasma membrane of cultured confluent brain-derived endothelial (bEND.3) cells was closely correlated with the increase in the transendothelial electrical resistance [4].
• Tracer experiments revealed that the barrier function of hypoxic retinal vasculature with depressed claudin-5 expression was selectively disrupted against small molecules, which is very similar to the phenotype of claudin-5-deficient mice [4].
• Wheatgerm agglutinin (WGA) increased 131I-HIV-1 penetration across the MBEC monolayer, consistent with absorptive endocytosis as the mechanism for HIV-1 penetration [8].

Anatomical context of Cldn5

• In addition, the transgenic hair follicles exhibit a decreased expression of K15 as well as some hair-specific keratins and express Cldn5 and Cldn18, which are not detectable in the wild type [10].
• In this study, we show that the tight junction protein, claudin-5, is present in cardiac muscle and localizes to the lateral membranes of cardiomyocytes in normal mice [1].
• These results indicate that claudin-5, but not claudin-12, is predominantly expressed in brain capillaries, and plays a key role in the appearance of barrier properties of brain capillary endothelial cells [9].
• Degradation of tight junction proteins, claudin-5 and occludin, and the basal lamina protein, laminin-alpha1, was less affected in the KO than in the WT [11].
• TMVCF is expressed abundantly in human adult lung, heart, and skeletal muscle, and transcripts can be detected at least as early as Day 9 of mouse development [12].

Associations of Cldn5 with chemical compounds

• Poly(A)+ RNA from MBEC expressed GSH uptake with significant (approximately 40-70%) Na+ dependency, whereas uptake expressed by poly(A)+ RNA from HepG2 and Cos-1 cells was Na+ independent [13].
• Plasma membrane vesicles from MBEC were separated into three fractions (30, 34, and 38% sucrose, by wt) by density gradient centrifugation [13].
• MBEC monolayers preloaded from the luminal surface with 131I-HIV-1 showed most of the virus was retained by the endothelial cells, while the remainder was effluxed mainly to the luminal surface [8].

Other interactions of Cldn5

• Immunogold labeling of ultrathin sections of brain as well as skeletal muscle revealed that the antigen strictly colocalizes in capillaries with the tight junction markers occludin, claudin-5, and ZO-1 [14].
• The serum-free media-induced decrease in permeability was correlated with an increase in claudin-5 and zonula occludens-1 immunofluorescence at cell-cell contracts [15].
• However, in some dermal vessels, claudin-5 expression was markedly decreased or absent in amount by double-immunofluorescence stainings with PECAM-1 and PAL-E [16].

Analytical, diagnostic and therapeutic context of Cldn5

• In the brain and lung, immunofluorescence microscopy with these polyclonal antibodies showed that claudin-5/TMVCF was exclusively concentrated at cell-cell borders of endothelial cells of all segments of blood vessels, but not at those of epithelial cells [2].
• Immunoreplica electron microscopy revealed that claudin-5/TMVCF was a component of TJ strands [2].
• In situ hybridization and immunocytochemical analyses revealed the presence of the MBEC1 mRNA and its protein product in brain capillary endothelial cells, as well as in a subset of other endothelial and epithelial cells [17].
• By Northern blot analysis, a 3.3-fold enhancement of mdr gene expression was observed in MBEC cultured on the PIC-fraction [18].
• Confocal microscopy of the animals with early and late skin lesions showed significant reduction in tight junction protein claudin-5 [19].

References