| RhoA和血清反应因子(SRF)介导E1A激活基因阻遏子诱导人血管平滑肌细胞分化 |
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| 引用本文： | 韩雅玲,徐红梅,闫承慧,胡 叶,康 建,刘海伟.RhoA和血清反应因子(SRF)介导E1A激活基因阻遏子诱导人血管平滑肌细胞分化[J].生物化学与生物物理进展,2006,33(5):438-445. |
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| 作者姓名： | 韩雅玲 徐红梅 闫承慧 胡 叶 康 建 刘海伟 |
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| 作者单位： | 1. 沈阳军区总医院全军心血管病研究所心内科,沈阳,110016
2. 大连市中心医院急诊科,大连,116033 |
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| 摘 要： | 为探讨E1A激活基因阻遏子(CREG)对人血管平滑肌细胞(VSMCs)分化的调控机制,应用重组逆转录病毒表达载体pLNCX2( )/CREG及pLXSN(-)/CREG制备稳定感染HITASY细胞模型,观察CREG蛋白过表达及表达抑制对人VSMCs分化的影响并探讨其调控机制.结果显示:pLNCX2( )/CREG稳定感染细胞呈分化表型,细胞细长变成组织样聚集生长趋势,细胞中CREG蛋白和平滑肌分化标志蛋白平滑肌α-肌动蛋白(SMα-actin)表达显著增加,同时SMα-actin相关调控因子——血清反应因子(SRF)入核转位,RhoA总蛋白表达上调,以Rho激酶特异性抑制剂Y-27632作用后,CREG诱导的SMα-actin表达下调的同时SRF出核转位;pLXSN(-)/CREG稳定感染的细胞体积变大,细胞极性消失,呈无序生长,细胞中CREG和SMα-actin蛋白表达显著降低,同时伴有SRF出核转位及RhoA总蛋白表达下调.免疫共沉淀分析发现,CREG蛋白能被分泌到VSMCs培养基中表达,并可与细胞膜受体6-磷酸甘露糖/胰岛素样生长因子Ⅱ型受体(M6P/IGF2R)发生直接相互作用.用蛋白磷酸酶PP2A特异性抑制剂okadaicacid减少M6P/IGF2R在细胞膜表面分布,可明显抑制CREG过表达引起的RhoA、SRF和SMα-actin表达.上述结果提示,在体外培养的人VSMCs中,CREG可能作为一种分泌型蛋白质通过与细胞膜受体M6P/IGF2R相互作用,依次激活SMα-actin蛋白相关调控因子RhoA和SRF引起SMα-actin表达增加,促进VSMCs向分化表型转换.
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| 关 键 词： | 阻遏蛋白 E1A 表型 细胞 血管平滑肌 人 |
| 收稿时间： | 2005-12-06 |
| 修稿时间： | 2/9/2006 12:00:00 AM |
The Cellular Repressor of E1A-stimulated Genes Promotes Human VSMCs Differentiation In vitro Mediated by RhoA and SRF |
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| HAN Ya-Ling,XU Hong-Mei,YAN Cheng-Hui,Hu Ye,KANG Jian and LIU Hai-Wei.The Cellular Repressor of E1A-stimulated Genes Promotes Human VSMCs Differentiation In vitro Mediated by RhoA and SRF[J].Progress In Biochemistry and Biophysics,2006,33(5):438-445. |
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| Authors: | HAN Ya-Ling XU Hong-Mei YAN Cheng-Hui Hu Ye KANG Jian and LIU Hai-Wei |
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| Institution: | Department of Cardiology, Shenyang General Hospital, Cardiovascular Research Institute of PLA, Shenyang 110016, China;Department of Cardiology, Shenyang General Hospital, Cardiovascular Research Institute of PLA, Shenyang 110016, China;Department of Cardiology, Shenyang General Hospital, Cardiovascular Research Institute of PLA, Shenyang 110016, China;Emergency Department of Dalian Municipal Central Hospital, Dalian 116033, China;Department of Cardiology, Shenyang General Hospital, Cardiovascular Research Institute of PLA, Shenyang 110016, China;Department of Cardiology, Shenyang General Hospital, Cardiovascular Research Institute of PLA, Shenyang 110016, China |
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| Abstract: | |
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| Keywords: | repressor protein E1A phenotype cell vascular smooth muscle human |
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