Direct Evidence That Hepatocyte Growth Factor Is A Hepatotrophic Factor for Liver Regeneration and Has A Potent Antihepatitis Effect In Vivo

ABSTRACT Hepatocyte growth factor, a potent mitogen for mature hepatocytes in vitro , seems to function as a hepatotrophic factor for liver regeneration. We examined the mitogenic effect of hepatocyte growth factor on mouse liver in vivo . The labeling index of hepatocytes was markedly increased when recombinant human hepatocyte growth factor was injected intravenously into mice subjected to 30% hepatectomy (control, 1.7% ± 0.1%; 1 μg hepatocyte growth factor, 6.4% ± 1.3%; 5 μg hepatocyte growth factor, 18.3% ± 0.2%) and into mice administered carbon tetrachloride (control, 12.7% ± 1.0%; 1 μg hepatocyte growth factor, 26.3% ± 2.8%) or α–naphthylisothiocyanate (control, 0.4% ± 0.1%; 1 μg hepatocyte growth factor, 3.8% ± 1.1%; 5 μg hepatocyte growth factor, 14.2% ± 2.0%). In addition, weights of the remnant livers in mice given hepatocyte growth factor 60 hr after 30% hepatectomy were significantly greater than those of untreated control mice (control, 0.93 ± 0.04 gm; 5 μg hepatocyte growth factor, 1.06 ± 0.04 gm). Hepatocyte growth factor prevented any marked increase in the serum levels of liver enzymes and bilirubin when it was administered to mice also treated with α–naphthylisothiocyanate (control: ALT, 394 ± 278 IU/L; lactate dehydrogenase, 2,644 ± 1,109 IU/L; bilirubin, 9.6 ± 2.6 mg/dl; and 5 μg hepatocyte growth factor: ALT, 135 ± 7.9 IU/L; lactate dehydrogenase, 1,672 ± 626 IU/L; bilirubin, 1.0 ± 0.8 mg/dl). Our findings show that intravenously injected hepatocyte growth factor stimulates the growth of hepatocytes in mouse liver and protects the integrity of hepatocytes in vivo against hepatitis caused by hepatotoxin. Thus hepatocyte growth factor may prove to be useful as a treatment for liver diseases as it is a hepatotrophic factor with a potent antihepatitis effect. (Hepatology 1992;16:1227-1235.)