DIFFERENTIAL EFFECT OF TRANSFORMING GROWTH-FACTOR-BETA ON PROTEOGLYCAN SYNTHESIS IN HUMAN EMBRYONIC LUNG FIBROBLASTS

The effect of transforming growth factor beta (TGF-beta) on the biosynthesis of individual proteoglycans (PGs) by human embryonic lung fibroblasts has been investigated using specific antibodies and cDNA probes. Human lung fibroblasts secrete the two small chondroitin/dermatan sulfate PGs, PG-I or biglycan (300 kDa) and, in a larger proportion, PG-II or decorin (130 kDa). Metabolic labeling experiments reveal that TGF-beta-induces selectively the expression of PG-I, whereas the level of PG-II remains unaltered. The effect of TGF-beta on PG-I and PG-II has been studied by immunoprecipitation and Northern blot analysis. Either at the core protein or mRNA level, a specific 5-fold increase in PG-I can be observed. TGF-beta-acts probably at the transcriptional level, as actinomycin D blocks completely the TGF-beta-induced proteoglycan synthesis. A low saturation density and a slower growth rate is also observed for TGF-beta-treated cells. The possible role of PG-I and PG-II as mediators of the growth inhibition caused by TGF-beta is discussed.