UP-REGULATED EXPRESSION OF FIBROBLAST-GROWTH-FACTOR (FGF) RECEPTORS BY TRANSFORMING GROWTH-FACTOR-BETA-1 (TGF-BETA-1) MEDIATES ENHANCED MITOGENIC RESPONSES TO FGFS IN CULTURED HUMAN LUNG FIBROBLASTS

Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional cy tokine that induces mesenchymal cell proliferation in vivo while inhib iting growth of most cells directly via serine-threonine receptor(s) b inding/activation in vitro. In this study, the ability of TGF-beta 1 t o regulate the receptor expression of classical mitogenic growth facto rs that bind receptor tyrosine kinases was examined. TGF-beta 1 marked ly increased the protein expression of the fibroblast growth factor (F GF) receptors FGFR-1 (Flg) and FGFR-2 (Bek) in a time- and dose-depend ent manner in human lung fibroblasts. This resulted in a potentiation of the mitogenic response of multiple FGF ligands that bind to these r eceptors, TGF-beta 1 had no effect on epidermal growth factor (EGF) or platelet-derived growth factor (PDGF)-beta receptor expression and th e mitogenic responses mediated by specific ligands for these receptors were not increased. These results demonstrate a novel action of TGF-b eta 1 to selectively upregulate the expression of FGF receptor family members leading to enhanced mitogenesis by FGFs. (C) 1998 Academic Pre ss.