锌指蛋白ZBTB20对血管平滑肌细胞分化及表型转换的调控作用

项目名称： 锌指蛋白ZBTB20对血管平滑肌细胞分化及表型转换的调控作用

项目编号： No.31471090

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 任安经

作者单位： 中国人民解放军第二军医大学

项目金额： 86万元

中文摘要： 血管平滑肌细胞(VSMC)的分化异常和表型转换是动脉粥样硬化等多种心血管病的发病基础，VSMC基因表达的转录水平调节在其分化和表型转换中起着关键作用。锌指蛋白ZBTB20，是申请人所在课题组自主克隆、并在国际上率先报道的新转录因子，在VSMC中高表达。为进一步了解ZBTB20 在血管中的生物学功能，我们利用Cre/loxp 技术建立了平滑肌特异性ZBTB20 敲除（SMCZB20KO）小鼠模型，发现该模型小鼠血管结构异常，舒张压明显降低。进一步检测显示SMCZB20KO小鼠VSMC分化出现明显异常，血管收缩功能明显下降。这些前期结果提示ZBTB20在VSMC的分化和功能中起着重要的作用。本课题拟在此基础上，深入分析ZBTB20在VSMC分化和表型转换中的作用及其机理，探索转录因子对VSMC的分化的网络化调控，为深入理解调控VSMC分化和表型转换的分子机制提供新的实验依据。

中文关键词： 转录因子；锌指蛋白；血管平滑肌细胞；细胞分化

英文摘要： Abnormal differentiation and phenotypic switching of vascular smooth muscle cells (VSMC) is the pathogenesis of atherosclerosis and other cardiovascular disease. Transcription regulation of gene expression plays a key role in the differentiation and phenotypic switching of VSMC. Zinc finger protein ZBTB20 is independently cloned by our group, and first reported on the international, which is highly expressed in VSMC. In order to further understand the biology function of ZBTB20 in vessel, we used the Cre/loxp technology to establish a smooth muscle specific ZBTB20 knockout mice (SMCZB20KO) model, and found obvious abnormal vascular structures in the mice, and significantly lower diastolic blood pressure was observed in SMCZB20KO mice. Further tests revealed vascular smooth muscle cell differentiation in SMCZB20KO mice appeared apparently abnormal, and vasoconstrictor function declined obviously. These preliminary results suggest ZBTB20 plays an important role in the differentiation and function of VSMC. In the present study, we further analysis the role of ZBTB20 in the differentiation and phenotypic switching of VSMC and clarify its mechanism. We want to provide a new experimental basis for the deep understanding of the molecular mechanism of differentiation and phenotypic switching of VSMC.

英文关键词： transcription factor;zinc finger protein;vascular smooth muscle cells;cell differentiation