Platelet-derived growth factor stimulated vascular smooth muscle cell proliferation and its molecular mechanism  

血小板源生生长因子刺激血管平滑肌细胞增殖及其分子机制(英文)

作　　者：李江[1] 黄韶玲[1] 郭兆贵[1] 

机构地区：[1]湖南医科大学分子药理研究室

出　　处：《Acta Pharmacologica Sinica》2000年第4期340-344,共5页中国药理学报（英文版）

摘　　要：AIM: To study the molecular mechanism of platelet-derived growth factor (PDGF)-BB-stimulated vascular smooth muscle cell ( VSMC) proliferation. METHODS: DNA synthesis was measured by [3H]thymidine incorporation. Phosphorylation of the 42- and 44-kDa Ca2 +-calmodulin dependent protein kinase (CCDPK) was measured by Western blotting method. The expression of c-myc specific mRNA was detected by in situ hybridization. RESULTS: PDGF-BB (2 μg·L-1) induced DNA synthesis and activated CCDPK in a concentration-dependent manner and a induced a marked c-myc mRNA expression. Egtazic acid (EGTA, 5 mmol·L-1), genistein (400 μmol·L-1) or PD 98059 (50 μmol·L-1) reduced PDGF-BB (2 μg · L-1)-induced CCDPK activities and inhibited VSMC [3H] thymidine incorporation ( P < 0.05). PD 98059 (50 μmol·L-1) also inhibited PDGF-BB (2 μg·L-1)-induced c-myc mRNA expression. CONCLUSION: PDGF stimulated VSMC proliferation by activation of p44/p42 CCDPK, which is mediated by Ca2+ and protein tyrosine kinase (PTK), and up-regulation of c-myc mRNA expression.目的:探讨血小板源生生长因子(PDGF-BB)刺激血管平滑肌细胞(VSMC)增殖及其分子机制。方法:用Western Blot法测定p44/p42 CCDPK活性。[~3H]脱氧胸腺嘧啶核苷酸掺入测定VSMC DNA合成。原位杂交检测c-myc mRNA的表达。结果:PDGF-BB诱导的磷酸化CCDPK蛋白表达和[~3H]脱氧胸腺嘧啶核苷酸掺入呈浓度依赖性,此作用可被PTK(抑制剂Gemscein,外钙络合剂依他酸和MEK抑制剂PD 98059抑制。PDGF-BB刺激可引起c-myc mRNA的明显表达,此作用可被PD 98059抑制。结论:PDGF-BB通过激活p44/p42 CCDPK,上调c-myc mRNA的表达从而促进VSMC增殖,其作用是由PTK和Ca^(2+)介导的。

关 键 词：Ca2+-calmodulin dependent protein kinase plate let-derived growth factor vascular smooth muscle cultured cells Western blotting in situ hybridization 

分 类 号：R33[医药卫生—人体生理学]