NOVEL CONTRIBUTIONS OF CLAUDIN-4 TO EPITHELIAL BARRIER REGULATION AND COLITIS

Abstract Intestinal barrier dysfunction is linked to human IBD and contributes progression of experimental, immune-mediated colitis. Claudin family tight junction proteins are critical determinants epithelial paracellular permeability function. Expression one these, claudin-2, a pore-forming claudin, specifically upregulated in IBD. We have shown that claudin-2 overexpression or, conversely, channel inhibition, augment or attenuate, respectively, colitis severity. sought understand claudin contributions function using vitro vivo models. Claudin-4 has been reduce cation vitro, leading the conclusion this protein barrier-forming claudin. found, however, that, absence expression, neither knockout nor claudin-4 affected Instead, suppressed pore by destabilizing polymers disrupting anchoring at junction. Thus, not but first pore-regulating Together with observations exacerbates antagonizes led us hypothesize intestinal would exacerbate Knockout mice were, protected from both DSS-induced chemical Conversely, transgenic exacerbated Preliminary studies suggest may limit collective migration wound repair. As whole, our require reconsideration functional classifications reveal unanticipated regulation The relationship between these functions downregulation remains be explored.