人脐带间充质干细胞微囊靶向调控Drp1恢复线粒体动态平衡促进肾脏缺血再灌注损伤修复的研究

项目名称： 人脐带间充质干细胞微囊靶向调控Drp1恢复线粒体动态平衡促进肾脏缺血再灌注损伤修复的研究

项目编号： No.81470919

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 朱英坚

作者单位： 上海交通大学

项目金额： 73万元

中文摘要： 缺血再灌注损伤是引起急性肾损害的主要原因之一，可引起急性肾功能衰竭，甚至后期肾纤维化和慢性肾功能衰竭。在损伤的发生和发展过程中，线粒体动态失衡和线粒体破碎是肾小管上皮细胞损伤和死亡的一个重要因素。当发生急性肾损伤时，Drp1作为介导线粒体动态失衡和线粒体破碎的一个重要因子，可快速激活并移位至线粒体，导致线粒体破碎，引起细胞损伤或死亡。干细胞技术的发展为肾损伤修复带来了新希望，干细胞微囊作为一种细胞与细胞间交流的媒介，可促进缺血再灌注损伤的修复。已有研究报道，microRNAs可通过抑制Drp1，减少线粒体的分裂和破碎，恢复线粒体动态平衡，促进心肌缺血再灌注损伤的修复。在前期工作基础上，我们希望揭示人脐带间充质干细胞微囊参与肾缺血再灌注损伤修复的一个重要机制，干细胞微囊可能通过microRNAs的横向传递，靶向调控Drp1，减少线粒体分裂破碎，恢复线粒体动态平衡，促进肾缺血再灌注损伤的修复

中文关键词： 间充质干细胞；微囊；动力相关蛋白1；线粒体动态；缺血再灌注损伤

英文摘要： Ischemia-reperfusion injury (IRI) is one of the main reasons of acute kidney injury(AKI).It can lead to acute renal failure, and even cause renal fibrosis and chronic renal failure in the late stage. Mitochondrial dynamic imbalance and mitochondrial fragmentation is a major contributor to renal tubular cell injury and death in the initiation and progression of AKI.As an impotant factor mediating mitochondrial dynamic imbalance and mitochondrial fragmentation, dynamin-related protein 1(Drp1) is activated rapidly following acute kidney injury and translocates to mitochondria leading to mitochondrial fragmentation and cell damage or death.The development of stem cell technology brings new hope to alleviate the kidney injury and promote the tissue repair.Microvesicles(MVs) derived from stem cells,as a meida in the communication between cells and cells,can promote the repair of kidney IRI. Recent studies have found that microRNAs can reduce mitochondrial fission and fragmentation, restore mitochondrial dynamic homeostasis through Drp1, and promote the repair of myocardial IRI. Based on our perivous studies, we hope to explore an important mechanism of microvesicles derived from human umbilical cord mesenchymal stem cells (HUCMSCs-MVs) involved in the repair of kidney IRI. HUCMSCs-MVs may reduce mitochondrial fission and fragmentation, restore mitochondrial dynamic homeostasis through horizontal transfer of microRNAs and trageting Drp1, promote the repair of kidney IRI.

英文关键词： mesenchymal stem cells;microvesicle;Dynamin-related protein 1;mitochondrial dynamic;ischemia-reperfusion injury