Expression of activin A is increased in cirrhotic and fibrotic rat livers

Background & Aims: Activin A, a member of the transforming growth factor (TGF)-β superfamily, recently has been reported to suppress DNA synthesis and to induce apoptosis of hepatocytes. These biological functions are similar to those of TGF-β1, which is overexpressed in liver cirrhosis. The aim of this study was to examine whether activin A is involved in liver cirrhosis and fibrosis. Methods: Liver cirrhosis or fibrosis was induced by intraperitoneal injections of dimethylnitrosamine or porcine serum into rats. The kinetics of activin A messenger RNA (mRNA) expression in cirrhotic and fibrotic livers and primary cultured rat hepatocytes were assessed by Northern blotting, and the localization of activin A was determined immunohistochemically. Modulation of type 1 collagen mRNA expression by activin A in rat cultured Ito/fat-storing cells and fibroblasts was also examined. Results: Northern blotting showed that activin A mRNA expression was enhanced in fibrotic livers. The numbers of hepatocytes expressing immunoreactive activin A were significantly greater, especially around the fibrotic areas. Activin A mRNA expression in cultured hepatocytes was increased significantly by TGF-β1 and by activin A itself. Furthermore, type 1 collagen mRNA expression in cultured cells was enhanced by activin A and TGF-β1 in a synergistic manner. Conclusions: Activin A is overexpressed in rat cirrhotic and fibrotic livers and may contribute to hepatic fibrogenesis. GASTROENTEROLOGY 1998;114:550-558