Differential expression of platelet-derived growth factor-alpha 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 deter mine whether Thy-1(-) and Thy-1(+) rat lung fibroblasts, which have distinc t and relevant phenotypes, differ in their proliferative responses to plate let-derived growth factor (PDGF) isoforms. Homogeneous populations of Thy-1 (-) and Thy-1(+) fibroblasts were found to proliferate equally in the prese nce of PDGF-BB, but PDGF-AA-mediated proliferation occurred only in Thy-1(- ) cells. This differential activity correlated with significantly higher ex pression of PDGF-alpha receptor in Thy-1(+) fibroblasts as shown by immunob lotting, immunofluorescence, and Northern blotting. There was a rapid incre ase in c-myc mRNA in Thy-1(-) but not in Thy-1(+) fibroblasts on stimulatio n with PDGF-AA and PDGF-BB. The PDGF-alpha receptor, which mediates signali ng by all PDGF isoforms, has been implicated in numerous clinical and exper imental forms of fibrosis and regulates lung morphogenesis. Differential ex pression of the PDGF-alpha receptor supports distinct roles for Thy-1(-) an d Thy-1(+) fibroblast populations in developmental and fibrotic processes i n the lung.