I-42 Regulation of a hepatitis C virus co-receptor claudin-1 in hepatocytes

Abstract

The polarization of hepatocytes involves formation of functionally distinct sinusoidal (basolateral) and bile canalicular (apical) plasma membrane domains that are separated by tight junctions. In murine livers, integral tight junction proteins claudin-1, -2, -3, -5, -7, -8, -12, -14 which can form tight junction strands are detected together with occludin, JAM, CAR and tricellulin, and claudin-1, -2, -3 are expressed in the bile canaliculus region of hepatocytes. In the livers (mouse, rat, human), claudin-1 and -3 are expressed in the whole liver lobule, whereas claudin-2 shows a lobular gradient increasing from periportal to pericentral hepatocytes. It is reported that downregulation of claudin-1 serves as a potential marker for a poor prognosis in HCC. More recently, it is found that the claudin-1 is a hepatitis C virus co-receptor with CD81. Thus, the study of regulation of claudin-1 in hepatocytes is very important for analysis of pathogenesis of hepatitis C virus infection. We have been studied for the regulation of tight junction proteins including claudin-1 in hepatocytes in vivo and in vitro. In this lecture, we present the regulation in expression and function of hepatic claudin-1 by growth factors (EGF, TGF-beta), cytokines (IL-1beta, oncostatin M) and partial hepatectomy via distinct signal transduction pathways.