从Notch信号通路探讨miR-124a对骨髓间质干细胞内源性胰岛分化潜能的调控机制及对糖尿病肾病的保护作用

项目名称： 从Notch信号通路探讨miR-124a对骨髓间质干细胞内源性胰岛分化潜能的调控机制及对糖尿病肾病的保护作用

项目编号： No.81200528

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： 孙吉平

作者单位： 西安交通大学

项目金额： 23万元

中文摘要： 骨髓间质干细胞（BMSCs）分化为胰岛素分泌细胞在糖尿病肾病修复过程中具有重要作用，如何提高其体外向胰岛素分泌细胞分化的效率是丞待解决的问题。本课题在前期研究基础上，提出"miR-124a可能通过抑制Notch信号通路激发BMSCs 内源性胰岛分化潜能，促进BMSCs体外分化为功能性胰岛"的新观点：筛选出调控胚胎胰腺发育的miRNAs- - miR-124a，通过模拟胚胎发育过程，激发BMSCs内源性胰岛分化潜能，促进BMSCs分化为功能性胰岛；在此基础上，通过Notch信号途径抑制剂构建类似于Notch信号敲除模型，探讨Notch信号通路在miR-124a调控BMSCs内源性胰岛分化潜能中的作用，进而通过动物模型研究BMSCs对糖尿病肾病的治疗作用及可能机制。本课题将miRNAs与干细胞成功结合，将为干细胞在糖尿病肾病细胞治疗中的应用提供一条新的思路。

中文关键词： 间质干细胞；糖尿病肾病；notch；胰岛；wnt

英文摘要： Chronic kidney disease is a leading cause of mortality and morbidity in western countries which affects about 11% of the adult population.Among such patients, 50% patients were induced by diabetic nephropathy,which is a complication of diabetes and is defined as progressive kidney disease caused by angiopathy of the capillaries supplying the kidney glomeruli. Bone mesenchymal stem cells (BMSCs) are multipotent, self-renewing cells that can be found in almost all postnatal organs and tissues. The main functional characteristics of BMSCs are their immunomodulatory ability, capacity for self-renewal, and differentiation into mesodermal tissues. BMSCs have been used for the treatment of diabetic nephropathy in nonobese diabetic/severely compromised immunodeficient mice. However,it is not clear whether BMSCs can propagate after engraftment in the kidney. In addition, successful BMSCs treatment of diabetic nephropathy could be explained by BMSCs competence to differentiate into insulin-producing beta cells followed by decrease of glycemia and glycosuria,factors important for damaging renal cells. However, such efficiency of trans- differentiation is low and there is lack of large scale therapeutic applications at present.We hypothesized that miR-124a might motivate the endogenous differentiation of BMSCs into insulin

英文关键词： mesenchymal stem cells；diabetic nephropathy；notch；islet；wnt