Differential expression of platelet-derived growth factor-α receptor by Thy-1− and Thy-1+ lung fibroblasts

Fibroblasts are heterogeneous with respect to surface markers, morphology, and participation in fibrotic responses. This study was undertaken to determine whether Thy-1− and Thy-1+ rat lung fibroblasts, which have distinct and relevant phenotypes, differ in their proliferative responses to platelet-derived growth factor (PDGF) isoforms. Homogeneous populations of Thy-1− and Thy-1+ fibroblasts were found to proliferate equally in the presence of PDGF-BB, but PDGF-AA-mediated proliferation occurred only in Thy-1− cells. This differential activity correlated with significantly higher expression of PDGF-α receptor in Thy-1− fibroblasts as shown by immunoblotting, immunofluorescence, and Northern blotting. There was a rapid increase in c-myc mRNA in Thy-1− but not in Thy-1+ fibroblasts on stimulation with PDGF-AA and PDGF-BB. The PDGF-α receptor, which mediates signaling by all PDGF isoforms, has been implicated in numerous clinical and experimental forms of fibrosis and regulates lung morphogenesis. Different...