Effects of platelet-derived growth factor and transforming growth factor-beta 1 on the synthesis of a large versican-like chondroitin sulfate proteoglycan by arterial smooth muscle cells.
Effects of platelet-derived growth factor and transforming growth factor-beta 1 on the synthesis of a large versican-like chondroitin sulfate proteoglycan by arterial smooth muscle cells.
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DOI：
10.1016/s0021-9258(19)47419-x
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发表时间：
1991-09
期刊：
影响因子：
--
通讯作者：
E. Schönherr;H. Järveläinen;L. Sandell;T. Wight
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文献类型：
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作者：
E. Schönherr;H. Järveläinen;L. Sandell;T. Wight
血小板衍生生长因子（PDGF）和转化生长因子- β 1 （tgf - β 1）增加猴子动脉平滑肌细胞将[35S]硫酸盐掺入蛋白多糖（PG），但对细胞增殖具有相反的作用。这两种生长调节肽的组合对PG的合成有叠加作用，但对细胞增殖无影响。刺激后硫酸盐结合的时间过程表明，这两种生长因子在12-18小时内使硫酸盐最大程度地结合到糖胺聚糖链中。受影响最大的PG是一个大的CSPG (Mr约为1.2 x 10(6))，它可以被一种针对versican的抗体免疫沉淀，versican是一种由人皮肤成纤维细胞合成的大CSPG。PDGF和tgf - β 1刺激后，该分子的水动力大小增加，但核心糖蛋白的大小（Mr约为450,000）保持不变。用任何一种生长因子处理都会导致PG核心糖蛋白的数量增加，这种增加与通过与编码变体的cDNA杂交鉴定的mRNA稳态水平的增加相关。这两种生长因子也增加了这种PG的糖胺聚糖链长度，这说明刺激后分子的水动力尺寸更大。相反，PDGF而不是tgf - β 1通过使硫酸软骨素6与硫酸软骨素4的比例加倍来改变附着在PG上的糖胺聚糖链的组成。这些结果表明，虽然这两种生长因子都增加了像CSPG这样的大聚糖的净合成，但它们对糖胺聚糖链结构的影响不同。这些翻译后修饰可能与细胞的生长状态有关。
Platelet-derived growth factor (PDGF) and transforming growth factor-beta 1 (TGF-beta 1) increase [35S]sulfate incorporation into proteoglycan (PG) by monkey arterial smooth muscle cells but have opposite effects on cell proliferation. The combination of these two growth regulatory peptides has an additive effect on PG synthesis but no effects on cell proliferation. The time course of sulfate incorporation after stimulation indicates that both growth factors cause maximal incorporation of sulfate into glycosaminoglycan chains by 12-18 h. The PG that is most affected is a large CSPG (Mr approximately 1.2 x 10(6)) which can be immunoprecipitated by an antibody against versican, a large CSPG synthesized by human skin fibroblasts. The hydrodynamic size of this molecule increases after PDGF and TGF-beta 1 stimulation, but the size of the core glycoprotein (Mr approximately 450,000) remains the same. Treatment with either growth factor leads to an increase in the amount of core glycoprotein for this PG. This increase correlates with an increase in the steady state level of mRNA identified by hybridization to a cDNA encoding versican. The two growth factors also increase the glycosaminoglycan chain length of this PG accounting for the greater hydrodynamic size of the molecule after stimulation. In contrast, PDGF and not TGF-beta 1 changes the composition of the glycosaminoglycan chains attached to this PG by doubling the ratio of chondroitin 6-sulfate to chondroitin 4-sulfate. These results indicate that although both of these growth factors increase the net synthesis of a large versican like CSPG, they differ in their effects on the structure of the glycosaminoglycan chains. These post-translational modifications may relate to the growth state of the cells.