Different Effects of Basic Fibroblast Growth Factor and Transforming Growth Factor-β on the Two Platelet-Derived Growth Factor Receptors' Expression in Scleroderma and Healthy Human Dermal Fibroblasts

Previous studies have demonstrated that platelet-derived growth factor (PDGF) α receptor expression is up-regulated by transforming growth factor-β1 (TGF-β1) in scleroderma dermal fibroblasts, but not in healthy control fibroblasts, We asked whether this selective effect in scleroderma cells was TGF-β1- specific or a general response by studying responses to other growth factors. In this study, we compared the expression of α and β PDGF receptor subunits (mRNA and protein levels) in these two cell types in response to basic fibroblast growth factor (bFGF) and TGF-β1 bFGF coordinately stimulated mRNA levels of α and β receptor subunits in healthy fibroblasts, but did not change PDGF receptor expression in scleroderma fibroblasts. Conversely, and in agreement with previous observations, TGF-β1 induced PDGF α receptor expression in scleroderma fibroblasts, but not in healthy fibroblasts. PDGF β receptor mRNA levels were induced to similar degrees by TGF-β1 in both cell types. PDGF α receptor protein levels correlated directly with mRNA levels, induced by bFGF only in healthy fibroblasts and by TGF-β1 only in scleroderma fibroblasts. However, PDGF β receptor protein levels were not altered by either growth factor in either cell type. Thus, the activated, state of scleroderma fibroblasts does not include receptor-signaling pathways to bFGF. This distinct pattern of expression of PDGF α receptors in scleroderma fibroblasts suggests a possible role for the coordinately expressed PDGF AA ligand/α receptor system in the development of fibrosis