miR17-92在肾脏缺血再灌注中的作用及机制研究

项目名称： miR17-92在肾脏缺血再灌注中的作用及机制研究

项目编号： No.81470980

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 林涛

作者单位： 四川大学

项目金额： 73万元

中文摘要： 肾脏缺血再灌注损伤（IRI）是影响移植肾短期及长期存活的重要因素，其损伤机制尚不清楚。我们发现小鼠肾脏IRI后多个miR-17-92簇的miRNA水平升高；后续实验发现miR-17-92高表达具有肾脏保护作用，具体机制不明。近来研究发现miR-17-92可以通过抑制凋亡来保护肿瘤细胞，生物信息学分析也发现其能够直接调控多个凋亡相关蛋白mRNA。因此我们提出在肾IRI中，miR-17-92可能通过抑制肾小管上皮细胞凋亡，改善肾功能。本项目拟首先通过检测移植肾及血液、尿液标本中miR-17-92表达图谱，证明miR-17-92与肾IRI的相关性，筛选具有调控作用的miRNA和凋亡因子；再通过细胞及动物实验验证miR-17-92在肾IRI的保护作用，确定发挥作用的miRNA，阐明下游具体信号通路，并探索miRNA mimics作肾IRI为潜在分子药物的可能性。

中文关键词： 缺血再灌注损伤；细胞凋亡；非编码RNA

英文摘要： Renal ischemia reperfusion injury (IRI) is associated with reduced short-term and long-term outcome of kidney transplantation. Furthermore, the mechanism is not well addressed. We found several miRNA of miR-17-92 cluster increased after IRI and miR-17-92 served as a protector in renal IRI. Data stem from oncology research identified miR-17-92 is an anti-apoptotic factor; additionally, bio-information analysis revealed that miR-17-92 can target the 3'UTR of several apoptosis trigger protein. Therefore, we hypothesized miR-17-92 down regulated apoptosis of tubule epithelia cell in renal IRI, leading to a better kidney function. In the present research, we will investigate the expression of miR-17-92 miR-17-92in biopsy of transplanted kidney, blood and urine, to establish and link to renal IRI and screening the effective miRNA and targeted apoptosis associated protein. Then we will further test the protective effect of miR-17-92 in renal IRI and find out the pivotal miRNA of miR-17-92 cluster and the signaling pathway. Finally, we will explore the miRNA mimics in renal IRI treatment.

英文关键词： Ischemia reperfusion injury;apoptosis;noncoding RNA