血小板源生长因子诱导核受体Nur77调节血管平滑肌细胞增殖
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武汉市卫生局科研基金项目[武卫2009(76文)]资助


Platelet Derived Growth Factor-Induced Nur77 Mediated Proliferation of Vascular Smooth Muscle Cells
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    摘要:

    目的研究血小板源生长因子诱导血管平滑肌细胞中核受体Nur77表达机制及其与血管平滑肌细胞增殖的关系,探讨阿托伐他汀对血小板源生长因子诱导的血管平滑肌细胞增殖和核受体Nur77表达的关系。方法分离培养鼠血管平滑肌细胞,分别与PD98059、阿托伐他汀、核受体Nur77 siRNA孵育后应用血小板源生长因子刺激,检测核受体Nur77、细胞外调节蛋白激酶表达;检测增殖细胞核抗原表达。结果血小板源生长因子诱导的血管平滑肌细胞中核受体Nur77通过ERK-MAPK信号途径表达。阿托伐他汀减少血小板源生长因子诱导的核受体Nur77表达,抑制血管平滑肌细胞增殖。在核受体Nur77沉默后的血管平滑肌细胞中,血小板源生长因子诱导的细胞增殖减少。结论血小板源生长因子诱导的血管平滑肌细胞增殖受核受体Nur77调控,阿托伐他汀降低核受体Nur77表达,减少血管平滑肌细胞增殖,这可能是他汀类药物抗细胞增殖的新的途径。核受体Nur77可能是减少再狭窄的新的治疗靶点。

    Abstract:

    Aim To investigate the expression of platelet derived growth factor induced nuclear receptor Nur77 mechanism and relationship with proliferation of vascular smooth muscle cell. Methods Vascular smooth muscle cells were isolated and cultured. The expression of nuclear receptor Nur77,extracellular regulated protein kinases,proliferating cell nuclear antigen induced by platelet derived growth factor were checked after incubation with PD98059,atorvastatin,Nur77 siRNA respectively. Results Platelet derived growth factor induced the expression of nuclear receptor Nur77 in vascular smooth muscle cell through ERK-MAPK signal pathway. Atorvastatin affected the expression of nuclear receptor Nur77 induced by platelet derived growth factor. Vascular smooth muscle cell proliferation was attenuated in nuclear receptor Nur77-deficient cells. Conclusion Nuclear receptor Nur77 regulated vascular smooth muscle cell proliferation induced by platelet derived growth factor. Atorvastatin decreased vascular smooth muscle cell proliferation by affecting the expression of nuclear receptor Nur77. This may be a new mechanism by which statins affected nuclear factor kappa B activity by regulating the nuclear receptor Nur77 expression. Down-regulation of nuclear receptor Nur77 suggests a novel therapy strategy for atherogenesis based on suppression of vascular smooth muscle cell proliferation.

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王丽岳, 李俊, 王珣, 熊晓昉, 董晓雁.血小板源生长因子诱导核受体Nur77调节血管平滑肌细胞增殖[J].中国动脉硬化杂志,2011,19(6):483~488.

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  • 收稿日期:2010-11-12
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