Differential Regulation of Platelet-Derived Growth Factor Genes in Fetal Rat Lung Fibroblasts

Abstract

There is increasing evidence to suggest that platelet-derived growth factor (PDGF), or PDGF-like molecules, play a role in fetal lung morphogenesis. The cellular sources of PDGF and its target cells within the fetal lung remain to be defined. In the present study, we investigated the developmental expression of PDGF and its cognate receptor genes in fetal rat lung fibroblasts. Northern analysis revealed that fetal lung fibroblasts express the PDGF A-chain, B-chain, and β-receptor genes. The cells actively translated these mRNAs into protein as demonstrated by immunocytochemistry and by metabolic labeling with [35S]methionine, followed by immunoprecipitation with specific PDGF-AA and -BB antibodies. Affinity cross-linking with 125I-labeled PDGF-BB demonstrated the presence of PDGF β-receptors on fetal lung fibroblasts. The developmental expression of the PDGF genes was examined in fibroblasts derived from the early canalicular (Day 19) to the early saccular stage (Day 21) of lung development (term - 22 days). PDGF A-chain gene expression was at a low but constant level during late gestation. No change in either the transcription rate or stability of the message for this gene was observed with advancing gestation. Despite these mRNA observations, PDGF-AA is the major secreted form in the medium of the fibroblasts. Expression of PDGF B-chain gene was greatest during the early canalicular stage (Day 19) and declined sharply thereafter. The greater expression of PDGF B-chain during the canalicular stage was due to a greater rate of transcription and a greater PDGF B-chain mRNA stability. The PDGF β-receptor gene was expressed at a lower but constant level in these cells during late gestation. The constant level of PDGF β-receptor mRNA could be attributed to a balanced increased synthesis of the message coupled to an increased breakdown of the transcript. These data indicate that fetal lung fibroblasts synthesize PDGF-AA, PDGF-BB, and PDGF β-receptor and that they regulate the developmental expression of these PDGF genes differently.