Effects of platelet-derived growth factor and other polypeptide mitogens on DNA synthesis and growth of cultured rat liver fat-storing cells

J Clin Invest. 1989 Dec;84(6):1786-93. doi: 10.1172/JCI114363.


In vitro and in vivo studies suggest that liver fat-storing cells (FSC) may play an important role in the development of liver fibrosis. We explored the effects of platelet-derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factor (TGF)-alpha and TGF-beta, and basic fibroblast growth factor (bFGF) on DNA synthesis and growth of rat liver FSC. PDGF, EGF, TGF-alpha, and bFGF induced a dose-dependent increase in DNA synthesis with a peak effect at 24 h. PDGF produced the most striking effect with a maximum 18-fold increase over control. EGF, TGF-alpha, and bFGF elicited a maximum three- to fourfold increase in DNA synthesis. Analysis of growth curves revealed a similar pattern of potency of the growth factors. TGF-beta did not affect DNA synthesis of FSC; however, TGF-beta markedly potentiated the stimulatory effects of both EGF and PDGF. FSC showed high specific binding of 125I-PDGF and Scatchard analysis revealed high affinity receptors with an apparent Kd of 2.3 x 10(-10) M. Our data suggest that PDGF is a key mitogen for FSC and that the coordinate release of other growth factors together with PDGF by inflammatory cells represents a potent potential stimulus for FSC proliferation in conditions of chronic self-perpetuating liver inflammation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • DNA / biosynthesis*
  • Drug Synergism
  • Epidermal Growth Factor / pharmacology
  • Fibroblast Growth Factors / pharmacology
  • Lipid Metabolism*
  • Liver / cytology
  • Liver / metabolism*
  • Male
  • Mitogens / pharmacology*
  • Platelet-Derived Growth Factor / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Transforming Growth Factors / pharmacology


  • Mitogens
  • Platelet-Derived Growth Factor
  • Fibroblast Growth Factors
  • Epidermal Growth Factor
  • Transforming Growth Factors
  • DNA