Cklf1促血管平滑肌细胞增殖和迁移过程中信号传导机制的研究

项目名称： Cklf1促血管平滑肌细胞增殖和迁移过程中信号传导机制的研究

项目编号： No.81370420

项目类型： 面上项目

立项/批准年度： 2014

项目学科： 医药、卫生

项目作者： 沈晨阳

作者单位： 中国医学科学院阜外医院

项目金额： 70万元

中文摘要： 我们前期研究发现趋化素样因子1（Chemokine-like factor 1，Cklf1）对血管平滑肌细胞（vascular smooth muscle cell，VSMC）具有明显的促迁移和增殖作用，而VSMC的迁移和增殖是外周血管疾病术后再狭窄的主要病理机制，该过程的细胞信号传导机制目前尚无人研究。通过前期预实验研究，我们推测Cklf1对VSMC的促增殖和迁移作用主要是通过NF-κB信号传导通路实现的。本课题旨在研究Cklf1参与该过程的信号传导机制及其调控机制，包括：①Cklf1是否引起NF-κB的活化；②因血管损伤或外源性刺激因子而激活的NF-κB对Cklf1表达的影响；③给予Cklf1作用于VSMC的主要信号传导因子的抑制剂后，观察VSMC增殖和迁移情况。④微流控技术模拟真实微环境下对以上传导通路进行验证,并对细胞表型转化进行初步的观察及研究。

中文关键词： 趋化素样因子1;血管平滑肌细胞;增殖;迁移;信号传导

英文摘要： Chemokine-Like Factor1 (Cklf1) has been tested with the effects on promoting migration and hyperplaisa of VSMC in our preliminary studies. Migration and hyperplaisa of VSMC is the most important pathological mechanism of peripheral vascular postoperative restenosis.However,signal tranduction mechanism of this pathophysiologcal process has not been explored, we highly suspected the effect of Cklf1 on VSMCs migration and hyperplasia is realized by the signal transduction of NF-κB according to our preliminary experiments. The purpose of this research is to characterize the signal transduction pathway of Cklf1 and NF-κB on VSMC migration and hyperplasia and explore underlying mechanisms:①whether Cklf1 can activate signal transduction pathway of NF-κB in VSMC or not；②Cklf1 expression under the influence of NF-κB actived by vascular injury or exogenous stimulators；③to observe the migration and hyperplasia of VSMC when given the inhibitors of signal transductive factor which is relatived with Cklf1。④to validate the above signal transduction and explore the transformation of VSMC phenotype in the microenviroment mimiced by microfluidic tecnique.

英文关键词： Cklf1;VSMC;hyperplasia;migration;signal transduction