Induction of hepatocyte growth by intraportal infusion of HGF into beagle dogs

Hepatocyte growth factor (HGF), originally identified as a potent mitogen for mature parenchymal hepatocytes, is a hepatotrophic factor involved in liver regeneration and is even essential for development of the liver. We report here that human recombinant HGF at a very low concentration and given intraportaly stimulated liver regeneration in dogs. In vitro, HGF dose-dependently stimulated DNA synthesis of primary cultured hepatocytes isolated from a dog. The maximal activity was twofold higher than that of epidermal growth factor, and insulin potentiated the mitogenic activity of HGF. When human recombinant HGF was infused through the portal vein into 30% partially hepatectomized dogs at 0.25 mu g/kg body weight in order to directly target the liver, HGF stimulated DNA synthesis of hepatocytes and liver weight at 72 h after the operation; labeling indices in saline- and HGF-injected groups were 0.75 and 1.82%, respectively, and the liver weights in saline- and HGF-injected groups were 302 and 374 g, respectively. Since HGF exerts potent antihepatitis activity as well as mitogenic activity, these results indicate that intraportal administration of HGF may be particularly important to enhance liver regeneration and prevent the severe hepatic insufficiently after hepatic surgery. (C) 1996 Academic Press, Inc.