INDUCTION OF LIVER GROWTH IN NORMAL MICE BY INFUSION OF HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR

Hepatocyte growth factor/scatter factor (HGF/SF) is a potent stimulato r of DNA synthesis in a variety of epithelial cells, including hepatoc ytes, and has been implicated in liver regeneration. We show here that combining dextran sulfate with HGF/SF markedly increases the plasma c oncentrations of HGF/SF that are achieved during intraperitoneal infus ion. Three days of administration of HGF/SF by this mechanism caused a dose-dependent increase in Liver wet weight. Mitotic figures were rar ely observed in control livers but were abundant in livers exposed to HGF/SF, and liver DNA content was elevated. Serum levels of triglyceri des, cholesterol, total protein, and albumin were also dose dependentl y increased, whereas alkaline phosphatase was reduced. From these data we conclude 1) that combining HGF/SF with dextran sulfate provides a novel method for delivering HGF/SF in a continuous manner, 2) that HGF /SF can induce liver growth in an intact animal, and 3) that HGF/SF-in duced liver enlargement is associated with changes in serum biochemist ry.