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

Abstract

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 TGE-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 receptor expression in scleroderma fibroblasts, but not in healthy fibroblasts. PDGF α receptor mRNA levels were induced to similar degrees by TGF-β1 in both cell types. PDGF a 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.