Fetal Lung Epithelial Cells Express Receptors for Platelet-derived Growth Factor

Abstract

There is increasing evidence to suggest that platelet-derived growth factor (PDGF) or PDGF-like molecules play a role in fetal lung morphogenesis. Our previous studies demonstrated that fetal lung epithelial cells respond mitogenically to exogenous PDGF, while fetal lung fibroblasts respond with increased glycosaminoglycan synthesis. To further study the target cells of PDGF in fetal rat lung, we investigated the presence and nature of PDGF receptors in fetal lung cells. Functional PDGF receptors were expressed on normal epithelial cells of fetal rat lung. All three isoforms of PDGF (AA, AB, and BB) were mitogenic for quiescent epithelial cells. Northern blot and protein analysis demonstrated the presence of PDGF alpha-receptor and PDGF beta-receptor. All isoforms of PDGF enhanced tyrosine kinase activity and stimulated receptor autophosphorylation. In contrast, fetal lung fibroblasts expressed only the PDGF beta-receptor. PDGF-AB and PDGF-BB, but not PDGF-AA, stimulated tyrosine kinase activity. No PDGF isoform was mitogenic for quiescent fibroblasts. However, PDGF-BB stimulated fibroblast proliferation on a collagen type I substratum in the presence of transferrin. Binding experiments with [125I]PDGF-AA and [125I]-PDGF-BB to epithelial cells and fibroblasts confirmed these observations.