Exosome中miR-1281通过组蛋白去乙酰化介导血管新生的机制研究

项目名称： Exosome中miR-1281通过组蛋白去乙酰化介导血管新生的机制研究

项目编号： No.81501939

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 胡斌

作者单位： 上海交通大学

项目金额： 18万元

中文摘要： 干细胞分泌的外泌体（Exosome）可以发挥与移植干细胞相类似的修复组织损伤功能，因其可高效传递miRNAs等活性物质到效应细胞，在促进血管新生和组织修复中发挥了重要作用。已有研究发现，缺氧环境下细胞分泌的Exosome中与血管新生密切相关的miRNAs特异性表达升高。我们的前期研究发现缺氧环境下培养干细胞分泌的Exosome中miRNAs出现了显著变化，尤其是miR-1281，进一步实验发现miR-1281可显著促进血管新生，生物信息学分析其靶向组蛋白去乙酰化酶。因此，本研究拟通过干扰或过表达干细胞中的miR-1281，明确Exosome传递miR-1281促进血管新生的功能，并研究miR-1281对HDACs及其下游效应基因的调控作用，明确miR-1281促进血管新生的分子机制。该研究将为优化Exosome辅助缺血性疾病的治疗提供理论依据。

中文关键词： 微小RNA；外泌体；血管新生；组蛋白去乙酰化

英文摘要： Exosome secreted by stem cells can perform similar functions with those of transplanted stem cells in tissue repair. By transferring miRNAs and other bioactivators to target cells efficiently, exosomes play important roles in angiogenesis and tissue healing. Recent studies indicate that some miRNAs which are highly related to angiogenesis are highly-expressed specifically in exosome secreted by cells under hypoxia conditions. Our previous results also found the expression levels of certain miRNAs in exosome from stem cells affected by hypoxia were significantly changed, eg. miR-1281. Further in vitro experiments demonstrated that miR-1281 did apparently promote angiogenesis. In addition, bioinformatics analysis suggests histone deacetylases (HDACs) could be the targets of miR-1281. As all mentioned above, we plan to change the expressing level of miR-1281 in stem cells and analyze the alterations of HDACs and their down-stream genes related to angiogenesis in vascular endothelial cells affected by the exosomes from miR-1281 manipulated stem cells. Our study will illuminate the underlying mechanism of exosomal miR-1281 from stem cells promoting angiogenesis by regulating HDACs in target vascular endothelial. And we believe that this will set up the theoretical base of exosome applying for the treatment of ischemic diseases.

英文关键词： microRNA;Exosome;Angiogenesis;histone deacetylation