INDUCTION OF HEPATOCYTE GROWTH BY INTRAPORTAL INFUSION OF HGF INTO BEAGLE DOGS

Hepatocyte growth factor (HGF), originally identified as a potent mito gen for mature parenchymal hepatocytes, is a hepatotrophic factor invo lved in liver regeneration and is even essential for development of th e liver. We report here that human recombinant HGF at a very low conce ntration and given intraportaly stimulated liver regeneration in dogs. In vitro, HGF dose-dependently stimulated DNA synthesis of primary cu ltured hepatocytes isolated from a dog. The maximal activity was twofo ld higher than that of epidermal growth factor, and insulin potentiate d the mitogenic activity of HGF. When human recombinant HGF was infuse d 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 stim ulated 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 pot ent antihepatitis activity as well as mitogenic activity, these result s 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.