HIPK2在高糖介导足细胞损伤中调节机制研究

项目名称： HIPK2在高糖介导足细胞损伤中调节机制研究

项目编号： No.81200526

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 靳远萌

作者单位： 上海交通大学

项目金额： 25万元

中文摘要： 足细胞损伤是糖尿病肾病重要病理改变之一，在启动肾小球硬化和蛋白尿产生中发挥关键性作用。近年研究已证实高糖刺激引起凋亡信号通路激活及纤维化改变是诱导足细胞损伤的重要机制。HIPK2是一种重要的转录辅助调节蛋白，是调控多种肾小管上皮细胞凋亡和纤维化损伤相关转录因子表达的关键性激酶，并初步证实对足细胞损伤也有一定调控作用。本课题以研究HIPK2在高糖介导足细胞损伤中的调节机制为目的，运用Real-time PCR、Western Blot、激酶活性分析、共聚焦显微镜、Tunel染色、肾皮质透射电镜等方法观察HIPK2表达改变对高糖刺激下足细胞凋亡相关蛋白、纤维化相关蛋白及其下游靶基因、裂隙膜相关蛋白、骨架相关蛋白表达的影响，明确HIPK2与足细胞损伤之间的关系，为糖尿病肾病的防治提供新的研究方向和治疗靶点。

中文关键词： HIPK2；足细胞；高糖；炎症；凋亡

英文摘要： Podocyte injury is an early feature of diabetic nephropathy and plays critical functional role in the development of proteinuria and glomerulosclerosis. Recent studies have proved that high glucose could cause apoptosis and fibrotic changes of podocyte. HIPK2 is an important kinase involved in transcriptional regulation of many genes which are responsible for pro-apoptotic and fibrotic changes of renal tubular epithelial cells. Furthermore, HIPK2 has also been shown to mediate podocyte injury, but underlying mechanism need to be further explored. The aim of this research is to investigate regulatory mechanism of HIPK2 in high glucose-mediated podocyte injury (including its roles in expression of apoptotic proteins, fibrotic proteins and genes, slit diaphragm-associated proteins and skeleton proteins), using methods including kinase assay, real-time PCR, western blot and etal. This research may supply new interference and treatment targets for diabetic nephropathy.

英文关键词： HIPK2；podocyte；high glucose；inflammation；apoptosis