Upregulated expression of fibroblast growth factor (FGF) receptors by transforming growth factor-beta1 (TGF-beta1) mediates enhanced mitogenic responses to FGFs in cultured human lung fibroblasts

Biochem Biophys Res Commun. 1998 Oct 20;251(2):437-41. doi: 10.1006/bbrc.1998.9443.

Abstract

Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that induces mesenchymal cell proliferation in vivo while inhibiting growth of most cells directly via serine-threonine receptor(s) binding/activation in vitro. In this study, the ability of TGF-beta1 to regulate the receptor expression of classical mitogenic growth factors that bind receptor tyrosine kinases was examined. TGF-beta1 markedly increased the protein expression of the fibroblast growth factor (FGF) receptors FGFR-1 (Flg) and FGFR-2 (Bek) in a time- and dose-dependent manner in human lung fibroblasts. This resulted in a potentiation of the mitogenic response of multiple FGF ligands that bind to these receptors. TGF-beta1 had no effect on epidermal growth factor (EGF) or platelet-derived growth factor (PDGF)-beta receptor expression and the mitogenic responses mediated by specific ligands for these receptors were not increased. These results demonstrate a novel action of TGF-beta1 to selectively upregulate the expression of FGF receptor family members leading to enhanced mitogenesis by FGFs.

Publication types

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

MeSH terms

  • Animals
  • Becaplermin
  • Cell Division / drug effects
  • Cell Line
  • Fibroblast Growth Factor 1
  • Fibroblast Growth Factor 10
  • Fibroblast Growth Factor 2 / pharmacology
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors / pharmacology*
  • Fibroblast Growth Factors / physiology
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Growth Substances / pharmacology
  • Humans
  • Kinetics
  • Lung / cytology
  • Platelet-Derived Growth Factor / pharmacology
  • Proto-Oncogene Proteins c-sis
  • Receptor Protein-Tyrosine Kinases / biosynthesis*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, Fibroblast Growth Factor, Type 2
  • Receptors, Fibroblast Growth Factor / biosynthesis*
  • Receptors, Fibroblast Growth Factor / genetics
  • Recombinant Proteins / pharmacology
  • Swine
  • Transforming Growth Factor beta / pharmacology*
  • Up-Regulation / drug effects

Substances

  • FGF7 protein, human
  • Fibroblast Growth Factor 10
  • Growth Substances
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins c-sis
  • Receptors, Fibroblast Growth Factor
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Fibroblast Growth Factor 2
  • Fibroblast Growth Factor 1
  • Fibroblast Growth Factor 7
  • Becaplermin
  • Fibroblast Growth Factors
  • FGFR1 protein, human
  • FGFR2 protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, Fibroblast Growth Factor, Type 2