项目名称: Egr-1与骨桥蛋白相互调控机制及在血管再狭窄中的作用
项目编号: No.30871074
项目类型: 面上项目
立项/批准年度: 2009
项目学科: 金属学与金属工艺
项目作者: 刘闺男
作者单位: 中国医科大学
项目金额: 29万元
中文摘要: 血管中膜平滑肌细胞(smooth muscle cell,SMC)向内膜下迁移与增殖是造成经皮冠状动脉介入治疗术后再狭窄(restenosis,RS)的主要原因之一。骨桥蛋白(osteopontin,OPN )、早期生长反应因子-1(early growth response factor-1,Egr-1)在介导SMC迁移、增殖和黏附过程中起着重要的作用,但二者的关系尚不清楚。我们在已有的工作基础之上,提出Egr-1可能直接和/或间接通过TGF-β35843;控OPN并且在他们之间可能存在一个放大的正反馈环。为证实该假设,我们在以往研究的基础上,对培养的SMC转染Egr-1、Egr-1特异的脱氧核酶ED5和siRNA OPN,用RT-PCR、Westernblot等方法分析转染前后,以及应用各种阻断剂前后,Egr-1与OPN的关系,以及这一关系的分子机制,为发现血管重塑的新靶点以及防治RS提供新思路。
中文关键词: 血管再狭窄;骨桥蛋白;Egr-1
英文摘要: Migrating towards the tunica intima and proliferation of the vascular smooth muscle cell(SMC)in the vascular tunica media is a primary cause of restenosis(RS) following percutaneous coronary interventions.Osteopontin(OPN) and early growth factor-1(Egr-1) play a significant role in mediating the process of migration、proliferation and adhension of the SMC, but relatively little knowledge is available on the relationship between OPN and Egr-1. On the basis of our previous data, we propose that OPN may be regulated by Egr-1 directly and/or indirectly by it via TGF-βd a magnifing positive feedback probably exist between them.To make sure of the hypothesis, in the light of our foregoing study, we use the Egr-1、the novel DNA enzyme targeting Egr-1(ED5)and interfer -ing RNA (siRNA) of OPN to transfect SMC. The aim of this study is to use RT-PCR、Westernblot and so on to observe the relationship between Egr-1 and OPN before and after the transfection and treating SMC with kinds of blocking agents and study its mechanism.The study will provide a new prospect to find a new target of vascular remodelling and for the RS.
英文关键词: restenosis;osteopontin;Egr-1