SIRT1对Nkx2.5的去乙酰化修饰在牵张诱导骨髓间充质干细胞向心肌细胞分化中的作用机制研究

项目名称： SIRT1对Nkx2.5的去乙酰化修饰在牵张诱导骨髓间充质干细胞向心肌细胞分化中的作用机制研究

项目编号： No.31300769

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 宋崴

作者单位： 北京航空航天大学

项目金额： 23万元

中文摘要： 牵张可诱导骨髓间充质干细胞（MSCs）向心肌细胞分化。Nkx2.5是调节心脏发育的重要转录因子，其乙酰化修饰与心肌发生密切相关。乙酰化修饰由乙酰转移酶和去乙酰化酶动态调节。目前Nkx2.5的去乙酰化修饰及其在心肌分化中的作用尚未见报道。申请人前期的研究显示：牵张上调Nkx2.5的表达，诱导MSCs向心肌细胞分化；同时下调MSCs中组蛋白去乙酰化酶SIRT1的表达；外源SIRT1与Nkx2.5在HEK293细胞中共定位及结合，提示SIRT1可能去乙酰化Nkx2.5调节MSCs向心肌细胞分化。鉴于此，本项目提出科学假设"牵张抑制SIRT1去乙酰化酶活性，促进Nkx2.5的乙酰化修饰，诱导MSCs向心肌细胞分化"，并拟研究牵张作用下MSCs中SIRT1对Nkx2.5的去乙酰化修饰调节，及二者的相互作用在心肌分化中的作用机制，为心脏组织工程及心脏相关疾病的治疗提供理论依据。

中文关键词： 牵张；骨髓间充质干细胞；分化；SIRT1；

英文摘要： Strain could induce cardiomyogenic differentiation of bone mesenchymal stem cells (MSCs). The transcription factor Nkx2.5 plays a crucial role in heart development and stem cell cardiomyogenesis. Recent studies indicated that the acetylation of Nkx2.5 was closely linked to regulating cardiac-specific gene expression during cardiac development. The acetylation status of a protein is maintained by the delicate dynamic equilibrium of two groups of enzymes, acetyltransferase and deacetylase. However, the function of Nkx2.5 deacetylation and its deacetylase in cardiomyogenic differentiation remains unclear. Our previous work showed that appropriate strain could induce the expression of Nkx2.5 gene and result in cardiomyogenic differentiation of MSCs. And the expression of SIRT1 decreased in cyclic strain induced cardiomyogenic differentiation of MSCs. The exogenously expressed Nkx2.5 and SIRT1 in HEK293 cells showed colocalization and interaction of these two proteins. So we evaluated that the decrease of SIRT1 deacetylase activity and the increase of the Nkx2.5 acetylation play important roles in strain-induced cardiomyogenic differentiation of MSCs. In this research, we will explore the role of Nkx2.5 deacetylation by SIRT1 in stretch-induced cardiomyogenic differentiation of MSCs. And it will contribute to cardic

英文关键词： strain；bone marrow mesenchymal stem cells；differentiation；SIRT1；