Molecular effect of hepatocyte membranes on the attenuation of hepatic stellate cell activation

Abstract

Background : Hepatocytes (Hep) contributes to a maintenance of “quiescent” phenotype of hepatic stellate cells (HSC) in co-culture system. We hypothesized that a direct binding to the hepatocyte membrane is essential for the maintenance of “quiescent” phenotype of HSCs and that there may be hepatocyte membrane factors that are involved in HSC deactivation. Methods : Cell membranes were isolated from wild-type mHep. Primary mHSC and human hepatic stellate cells (HHSteC) were cultured with the hepatocyte-membranes and subjected to the morphological observation using time-lapse imaging and gene expression analysis. Results : mHSCs cultured on hepatocyte membranes showed dendrite-rich morphology, a “quiescent” phenotype, and expressions of HSC-activation markers, Acta2 and Col1a1 were suppressed in these cells compared to those in mHSCs following normal plate cultures. In HHSteC with hepatocyte membranes, ACTA2 and COL1A1 expressions were suppressed, while the HSC-quiescent marker, MMP1 mRNA expression increased in dose-dependent manners. Conclusion : This study suggests the presence of hepatocyte membrane factors that are involved in maintaining the ‘quiescent’ phenotype of HSCs. We further investigate the pathophysiological role of hepatocyte membranes.