CD131在CEPO抑制高糖诱导的肾小管上皮细胞凋亡中的作用及机制

项目名称： CD131在CEPO抑制高糖诱导的肾小管上皮细胞凋亡中的作用及机制

项目编号： No.81500639

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： 党建中

作者单位： 武汉大学

项目金额： 18万元

中文摘要： EPO及其衍生物被证实可通过抗细胞凋亡等效应发挥非血液学的组织保护作用，CEPO半衰期较长，同时无造血活性，被认为是具有更好临床应用前景的EPO衍生物之一。与EPO需要通过EPOR-EPOR同二聚体介导发挥促红细胞生成作用不同，近期有研究发现EPO及其衍生物发挥组织保护作用可能需要通过EPOR-CD131异二聚体介导，但目前对这一受体系统的存在与否仍有争论。在前期的工作中，我们发现大鼠肾小管细胞表达EPOR，且预实验显示CEPO可抑制高糖诱导的大鼠肾小管细胞凋亡。我们推测肾小管细胞内存在EPOR-CD131异二聚体，CEPO可以通过EPOR-CD131介导，抑制糖尿病时高血糖状态导致的肾小管细胞凋亡，发挥肾脏保护作用。为验证这一假说，本项目拟通过细胞培养、动物实验研究CEPO对高糖诱导的肾小管细胞凋亡的影响及CD131在此过程中的可能作用，为探索新的糖尿病肾脏病治疗方案提供实验依据。

中文关键词： 氨甲酰促红细胞生成素；糖尿病肾脏病；肾小管细胞；CD131；凋亡

英文摘要： Erythropoietin and its derivatives have been confirmed to play non hematological tissue protective effects through anti apoptosis. Carbamylated erythropoietin, which has a long half-life, and has no hematopoietic activity, is considered to be one of the erythropoietin derivatives with better prospects for clinical application. Unlike its erythropoiesis effect, which need a homodimer of two erythropoietin receptors, erythropoietin and its derivatives need heterodimers consisted of erythropoietin receptor and CD131 to play non hematological tissue protective effects in the central nervous system and cardiovascular system. However, there is still controversy about the existence of the heterodimers in above tissues. In previous work, we found the expression of erythropoietin receptor in rat renal tubular cells, and our preliminary experiment showed carbamylated erythropoietin can inhibit rat renal tubular cells apoptosis induced by high glucose. So, we hypothesize the presence of the heterodimers consisted of erythropoietin receptor and CD131 in renal tubular cells, and carbamylated erythropoietin can inhibit renal tubular cells apoptosis induced by high glucose through the heterodimers in vitro and in vivo, thereby play a role in renal protection in diabetic rats. To demonstrate this hypothesis, we will observe the effect of carbamoyl erythropoietin on renal tubular cell apoptosis induced by high glucose in vitro and in vivo, and the possible role of CD131 in this process. Finally, this work will provide experimental basis for the exploration of new treatments for diabetic kidney disease.

英文关键词： carbamylated erythropoietin;diabetic kidney disease; renal tubular cells ;CD131;apoptosis