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 stimulator of DNA synthesis in a variety of epithelial cells, including hepatocytes, and has been implicated in liver regeneration. We show here that combining dextran sulfate with HGF/SF markedly increases the plasma concentrations of HGF/SF that are achieved during intraperitoneal infusion. Three days of administration of HGF/SF by this mechanism caused a dose-dependent increase in liver wet weight. Mitotic figures were rarely observed in control livers but were abundant in livers exposed to HGF/SF, and liver DNA content was elevated. Serum levels of triglycerides, cholesterol, total protein, and albumin were also dose dependently 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-induced liver enlargement is associated with changes in serum biochemistry.
Roos
F
F
Department of Endocrine Research, Genentech, Incorporated, South San Francisco, California 94080.
Ryan
A M
AM
Chamow
S M
SM
Bennett
G L
GL
Schwall
R H
RH
D000818:Animals; D016264:Dextran Sulfate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D007260:Infusion Pumps; D007274:Injections, Intraperitoneal; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H
D004338:Drug Combinations; D017228:Hepatocyte Growth Factor; D016264:Dextran Sulfate