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.
Copyright 1998 Academic Press.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Becaplermin
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Cell Division / drug effects
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Cell Line
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Fibroblast Growth Factor 1
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Fibroblast Growth Factor 10
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Fibroblast Growth Factor 2 / pharmacology
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Fibroblast Growth Factor 7
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Fibroblast Growth Factors / pharmacology*
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Fibroblast Growth Factors / physiology
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Fibroblasts / cytology
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Fibroblasts / drug effects
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Fibroblasts / metabolism
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Filaggrin Proteins
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Growth Substances / pharmacology
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Humans
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Kinetics
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Lung / cytology
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Platelet-Derived Growth Factor / pharmacology
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Proto-Oncogene Proteins c-sis
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Receptor Protein-Tyrosine Kinases / biosynthesis*
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Receptor Protein-Tyrosine Kinases / genetics
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Receptor, Fibroblast Growth Factor, Type 1
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Receptor, Fibroblast Growth Factor, Type 2
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Receptors, Fibroblast Growth Factor / biosynthesis*
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Receptors, Fibroblast Growth Factor / genetics
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Recombinant Proteins / pharmacology
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Swine
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Transforming Growth Factor beta / pharmacology*
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Up-Regulation / drug effects
Substances
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FGF7 protein, human
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FLG protein, human
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Fibroblast Growth Factor 10
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Filaggrin Proteins
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Growth Substances
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Platelet-Derived Growth Factor
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Proto-Oncogene Proteins c-sis
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Receptors, Fibroblast Growth Factor
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Recombinant Proteins
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Transforming Growth Factor beta
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Fibroblast Growth Factor 2
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Fibroblast Growth Factor 1
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Fibroblast Growth Factor 7
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Becaplermin
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Fibroblast Growth Factors
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FGFR1 protein, human
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FGFR2 protein, human
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Receptor Protein-Tyrosine Kinases
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Receptor, Fibroblast Growth Factor, Type 1
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Receptor, Fibroblast Growth Factor, Type 2