PLATELET-DERIVED GROWTH-FACTOR AND TRANSFORMING GROWTH-FACTOR-BETA-1 DIFFERENTIALLY AFFECT THE SYNTHESIS OF BIGLYCAN AND DECORIN BY MONKEY ARTERIAL SMOOTH-MUSCLE CELLS

Platelet-derived growth factor (PDGF) and transforming growth factor-beta1 (TGF-beta1), two growth-regulatory peptides with opposite effects on arterial smooth muscle cell (ASMC) proliferation, were examined for their influence on the synthesis of two small chondroitin sulfate/dermatan sulfate proteoglycans (CS/DS PGs) called biglycan and decorin. Quiescent ASMCs treated with either PDGF or TGF-beta1 for 24 hours increased [S-35]sulfate incorporation into biglycan 3.3- and 2.9-fold, respectively, whereas the incorporation of [S-35]sulfate into decorin was not significantly affected. Treatment with TGF-beta1 but not PDGF more than doubled the steady-state level of messenger RNA (mRNA) transcripts hybridizing to a complementary DNA (cDNA) encoding biglycan. Both growth factors had little or no effect on steady-state levels of mRNA transcripts hybridizing to a decorin cDNA. Incorporation of [S-35]sulfate into biglycan glycosaminoglycan (GAG) was maximal by 12 to 18 hours after either PDGF or TGF-beta1 addition. Both PDGF and TGF-beta1 increased the molecular sizes of biglycan and decorin. This increase was a result of the synthesis of longer GAG chains substituted on the core proteins of both PGs. PDGF but not TGF-beta1 led to an increase of more than twofold in the ratio of 6'- to 4'-sulfated disaccharides in these newly synthesized GAG chains. These results indicate that PDGF and TGF-beta1 have specific but different effects on the synthesis of small CS/DS PGs by monkey ASMCs in culture.