ARB抑制miR-193a表达促进早期糖尿病肾病壁层上皮细胞-足细胞转分化研究

项目名称： ARB抑制miR-193a表达促进早期糖尿病肾病壁层上皮细胞-足细胞转分化研究

项目编号： No.U1504805

项目类型： 联合基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 高丹

作者单位： 郑州大学

项目金额： 27万元

中文摘要： 足细胞损伤导致糖尿病肾病大量蛋白尿，而足细胞是终极分化细胞，一旦损伤很难再生，我们前期研究中观察到壁层上皮细胞(PEC)可转分化修复足细胞，ARB可促进转分化过程，但作用机制还有待于进一步探讨。最新研究发现miR-193a表达被下调后可诱导PEC高表达WT-1，促进其向足细胞转分化。为此我们提出假说：糖尿病肾病时ARB抑制PEC表达miR-193a诱导PEC向足细胞转分化。本研究拟以自发性2型糖尿病db/db鼠及体外培养足细胞、PEC为研究对象，以足细胞标志物WT-1、synaptopodin、GLEEP1和PEC标志物claudin1、CD44以及miR-193a的表达为观察指标，采用real timePCR、western blot、细胞转染等手段，观察miR-193a在早期糖尿病肾病PEC转分化对足细胞的修复过程中发挥的作用，以miR-193a为新视点为延缓糖尿病肾病进展提供新思路。

中文关键词： 糖尿病肾病；足细胞损伤/修复；壁层上皮细胞；microRNA-193a；

英文摘要： Podocyte injury is a central pathomechanism to diabetic nephropathy. Podocyte, specialized terminally differentiated cells, is difficult to regenerate. We observed that parietal epithelial cell(PEC) has the potential ability to repair podocyte in In our previous study, ARB can promote the PEC-podocyte transition. But the mechanism remains to be further explored. The new report found that miR-193a expression downregulation can induce high expression of PEC WT-1 then promote the transition to podocyte. Therefore, we put forward the hypothesis: ARB promote Parietal epithelial cell-podocyte transition by downregulating microRNA-193a expression in Diabetic nephropathy. In this study, based on db/db mice and podocyte PEC in vivo, podocyte markers WT-1, synaptopodin, GLEEP1and PEC markers claudin1, CD44 and miR-193a expression were observed, with real timePCR, Western blot, cell transfection, we investigated whether miR-193a play a role in PEC-podocyte transition in early diabetic nephropathy, with miR-193a as a new viewpoint to provide new ideas for delaying the progression of diabetic nephropathy.

英文关键词： diabetic nephropathy;podocyte injury/repair;parietal epithelial cell;microRNA-193a