Schönherr E, Järveläinen H T, Kinsella M G, Sandell L J, Wight T N
Department of Pathology, School of Medicine, University of Washington, Seattle 98195.
Arterioscler Thromb. 1993 Jul;13(7):1026-36. doi: 10.1161/01.atv.13.7.1026.
Platelet-derived growth factor (PDGF) and transforming growth factor-beta 1 (TGF-beta 1), 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-beta 1 for 24 hours increased [35S]sulfate incorporation into biglycan 3.3- and 2.9-fold, respectively, whereas the incorporation of [35S]sulfate into decorin was not significantly affected. Treatment with TGF-beta 1 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 [35S]sulfate into biglycan glycosaminoglycan (GAG) was maximal by 12 to 18 hours after either PDGF or TGF-beta 1 addition. Both PDGF and TGF-beta 1 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-beta 1 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-beta 1 have specific but different effects on the synthesis of small CS/DS PGs by monkey ASMCs in culture.
血小板衍生生长因子(PDGF)和转化生长因子-β1(TGF-β1)是两种对动脉平滑肌细胞(ASMC)增殖具有相反作用的生长调节肽,研究了它们对两种称为双糖链蛋白聚糖和核心蛋白聚糖的小硫酸软骨素/硫酸皮肤素蛋白聚糖(CS/DS PGs)合成的影响。用PDGF或TGF-β1处理静止的ASMC 24小时,分别使[35S]硫酸盐掺入双糖链蛋白聚糖增加3.3倍和2.9倍,而[35S]硫酸盐掺入核心蛋白聚糖则未受到显著影响。用TGF-β1而非PDGF处理使与编码双糖链蛋白聚糖的互补DNA(cDNA)杂交的信使RNA(mRNA)转录本的稳态水平增加了一倍多。两种生长因子对与核心蛋白聚糖cDNA杂交的mRNA转录本的稳态水平几乎没有影响。在添加PDGF或TGF-β1后12至18小时,[35S]硫酸盐掺入双糖链蛋白聚糖糖胺聚糖(GAG)达到最大值。PDGF和TGF-β1均增加了双糖链蛋白聚糖和核心蛋白聚糖的分子大小。这种增加是由于在两种PGs的核心蛋白上合成了更长的GAG链。PDGF而非TGF-β1导致这些新合成的GAG链中6'-硫酸化二糖与4'-硫酸化二糖的比例增加了两倍多。这些结果表明,PDGF和TGF-β1对培养的猴ASMC中小CS/DS PGs的合成具有特定但不同的影响。