Effects of hepatocyte growth factor on the growth and metabolism of human hepatocytes in primary culture

Hepatology. 1995 May;21(5):1248-54.

Abstract

The effect of recombinant human hepatocyte growth factor (h-rHGF), a potent mitogen for hepatocytes, was investigated in primary cultures of human hepatocytes. Here, we describe a series of experiments to investigate the kinetics of its mitogenic action, as well as its metabolic effects on cultured human hepatocytes. The h-rHGF is a potent signal for initiating DNA synthesis in human hepatocytes, with maximal stimulatory effects at 10 ng/mL (0.1 pmol/L). The kinetics of DNA synthesis showed a lag of about 48 to 72 hours, followed by a maximum at 96 hours. At least 48 hours of continuous exposure to h-rHGF are required to initiate DNA synthesis in quiescent human hepatocytes. Cell cycle analysis by flow cytometry showed that most of quiescent 2c cells have left G0/G1 and entered the cell cycle (S and G2/M phases) by 96 hours of continuous exposure to h-rHGF. When compared with other growth factors, h-rHGF was a much more potent mitogen. The effects of 10 ng/mL (0.1 pmol/L) h-rHGF on DNA synthesis were only achieved by 1.5 pmol/L epidermal growth factor (EGF), 0.1 mumol/L insulin, or 1 mumol/L glucagon. It is noteworthy that the effect of h-rHGF was potentiated by glucagon but not by insulin or EGF. The stimulatory effect of HGF on DNA synthesis was gradually inhibited by h-rHGF transforming growth factor beta (TGF-beta) in the range 1 to 10 ng/ml. The HGF also influenced the expression of other hepatic genes.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Reaction / blood
  • Adult
  • Aged
  • Blood Proteins / analysis
  • Cell Division / drug effects
  • Cells, Cultured
  • DNA / biosynthesis
  • Dose-Response Relationship, Drug
  • Female
  • Glycogen / metabolism
  • Growth Substances / pharmacology
  • Hepatocyte Growth Factor / pharmacology*
  • Hormones / pharmacology
  • Humans
  • Kinetics
  • Liver / cytology
  • Liver / drug effects*
  • Liver / metabolism*
  • Male
  • Middle Aged
  • Recombinant Proteins

Substances

  • Blood Proteins
  • Growth Substances
  • Hormones
  • Recombinant Proteins
  • Hepatocyte Growth Factor
  • Glycogen
  • DNA