DIFFERENTIAL EFFECT OF PLATELET-DERIVED GROWTH-FACTOR ON GLYCOSAMINOGLYCAN SYNTHESIS BY FETAL-RAT LUNG-CELLS

Lung morphogenesis is in part regulated by extracellular matrix (ECM), and cytokines may indirectly control lung development via modulation of ECM. In the present study, we investigated the effect of different platelet-derived growth factor (PDGF) isoforms AA, AB, and BB on the synthesis of glycosaminoglycans (GAG) by fetal rat lung cells. Independent of gestational age, PDGF-BB, but not PDGF-AA or -AB, stimulated GAG synthesis of fetal lung fibroblasts. In contrast, GAG synthesis by epithelial cells was not affected by any of the PDGF molecules. The stimulatory effect of PDGF-BB on fibroblast GAG biosynthesis was dose (>10 ng/ml) and time (>8 h) dependent. The relative proportion of the individual GAG molecules was not altered by PDGF-BB exposure. Blockage of tyrosine kinase activity with staurosporine did abolish the effect of PDGF-BB on fibroblast GAG formation. Actinomycin D and cycloheximide did not abrogate the PDGF-BB effect, suggesting that no new RNA or protein synthesis is required. The proteoglycan synthesis blocker, beta-D-xyloside, also did not inhibit the PDGF-BB action on fibroblast GAG synthesis. These data suggest that the effect of PDGF on GAG synthesis is cell type and isoform specific and is most likely a direct effect on the GAG chain elongation enzymes.