内皮祖细胞源性微粒microRNA抑制内皮间质转化改善心脏纤维化的机制研究

项目名称： 内皮祖细胞源性微粒microRNA抑制内皮间质转化改善心脏纤维化的机制研究

项目编号： No.81500307

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： 麦憬霆

作者单位： 中山大学

项目金额： 18万元

中文摘要： 心脏纤维化（CF）是心力衰竭领域的研究热点，新近认为内皮间质转化（EndMT）是其重要途径。有报道内皮祖细胞（EPC）可通过分泌微粒传递蛋白和RNA而抑制纤维化。我们也发现EPC微粒可减轻主动脉缩窄（TAC）诱导的CF及心脏EndMT水平，但其机制尚不清楚。此外，我们通过用假手术及心衰小鼠血清孵育的EPC其微粒处理内皮细胞，发现前者抑制EndMT作用明显强于后者，以RNA酶处理微粒后抑制作用均消失，说明EPC微粒主要通过RNA起作用。对EPC微粒行miRNA芯片发现15个miRNA在假手术血清孵育的EPC微粒中表达明显高于心衰血清孵育的EPC微粒，提示EPC 微粒通过miRNA抑制EndMT。故本项目拟通过体内TAC及体外TGF-β诱导的EndMT模型，在候选miRNA中筛选出目标miRNA，验证它在EPC微粒抑制EndMT中的作用并寻找其靶基因，为干预EndMT途径实现抗CF提供新思路。

中文关键词： 内皮祖细胞；微粒；内皮间质转化；心脏纤维化；微小RNA

英文摘要： Increasing studies observed that EndMT played pivotal role in the progression of cardiac fibrosis(CF). Previous study found that endothelial progenitor cell (EPC)-derived microvesicles(MV) could inhibit CF by transporting protein and RNA. Our data also indicated that EPC-MV could inhibit CF in transverse aortic constriction (TAC) model. However, the underlying mechanism was unclear. Hence, our project aimed to explore the role of EndMT in EPC-MV mediating CF inhibition. EPC was stimulated with the serum from sham-operation mice and TAC-induced heart failure mice, and then EPC-MV were collected respectively(sham-EPC-MV and hf-EPC-MV). The data showed that sham-EPC-MV had a more potent effect in suppressing TGF-β induced EndMT, which could be abolished by pretreating EPC-MV with RNAse. These data indicated that RNA containing in EPC-MV might mediate EndMT inhibition. Furthermore, miRNA array between two types of MV was done. The data showed that fifteen miRNA were significant higher in sham-EPC-MV than in hf-EPC-MV. Hence, this project aimed to screen out the key miRNA which mediated the effect of EPC-MV in suppressing EndMT. Moreover, the target gene of miRNA was explored. This project would help to explain the therapeutic mechanism of EPC-MV in CF and also highlight the role of EndMT in this issue.

英文关键词： endothelial progenitor cell;Microvesicle;endothelial-mesenchymal transition;cardiac fibrosis;microRNA