表皮生长因子受体在肥胖相关性肾病中的作用及机制研究

项目名称： 表皮生长因子受体在肥胖相关性肾病中的作用及机制研究

项目编号： No.81500657

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： 钟鹏

作者单位： 温州医科大学

项目金额： 18万元

中文摘要： 肥胖引起多种并发症，包括肥胖相关性肾病（ORG），其中慢性炎症和纤维化是介导ORG发生发展的重要病理过程。虽然肥胖已成流行趋势，但是对ORG的基础和临床研究还有待加强。表皮生长因子受体（EGFR）是重要的肿瘤治疗靶点，近年研究发现EGFR还介导了胰岛素抵抗、动脉粥样硬化和糖尿病肾病等慢性疾病的发生发展。我们前期研究发现：口服EGFR抑制剂AG1478和542在高脂饮食诱导的肥胖小鼠中显著缓解肾损伤，并伴随着肾脏炎症反应的下降。因此本项目假设，EGFR介导了高血脂诱导的炎症反应和肾损伤，抑制EGFR可以防治ORG。本项目中，我们拟在细胞层面确证高脂激活EGFR、以及EGFR介导高脂炎症反应从而导致肾细胞损伤的分子机制；利用高脂饮食、肾脏特异性EGFR敲除小鼠验证EGFR在ORG中的作用。项目将阐明EGFR在肥胖肾炎症反应和ORG中的介导作用和机制，为防治ORG提供新的靶点。

中文关键词： 表皮生长因子受体；肥胖；肾损伤；炎症；纤维化

英文摘要： Obesity cause a variety of complications, including obesity-related glomerulopathy(ORG), chronic inflammation and fibrosis mediated the pathological process of ORG. Although obesity has become a popular trend, the basic and clinic reaserch of ORG is still to be strengthened. Epidermal growth factor receptor (EGFR) is an important target for tumor therpy, recent studies have found that EGFR can mediate the insulin resistance, the process of atherosclerosis, diabetic nephropathy and other chronic diseases. Our previous studies had found that orally giving EGFR inhibitors AG1478 and 542 significantly alleviated renal damage and accompanied by the decline of renal inflammatory reaction in high fat diet induced obese mice. In this project we propose the following hypothesis, EGFR mediated inflammatory response and renal injury induced by high fat, inhibiting EGFR can prevent ORG. In this project, we will confirmed high fat activated EGFR and the molecular mechanism of EGFR mediated high fat inflammation leading to renal cell injury in vitro; using high fat diet, kidney specific EGFR knockout mice model to verify the effects of EGFR in ORG. This project will explain the effects and mechanism of EGFR in obesity renal inflammatory response and ORG, providing new targets for prevention and treatment of ORG.

英文关键词： epidermal growth factor receptor ;obesity;kidney injury;inflammation;fibrosis