MiR-212/203调控糖网病神经节细胞凋亡的作用及机制研究

项目名称： MiR-212/203调控糖网病神经节细胞凋亡的作用及机制研究

项目编号： No.81470641

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： 吴强

作者单位： 上海交通大学

项目金额： 73万元

中文摘要： MiRNAs是一种非编码小RNA，多个miRNAs可能参与糖尿病视网膜病变（DR）神经节细胞（RGC）凋亡调控。我们前期研究发现miR-212和-203在DR发病过程中有显著差异表达。MiR-212和-203在众多疾病中有凋亡调控作用，但对DR的RGC凋亡调控及机制尚不清楚。本课题拟应用转基因及荧光素酶报告等分子生物学技术研究:1.验证miR-212和-203是否对DR的RGC具有凋亡调控作用；2.miR-212是否通过靶基因p300、slit2及p300/p53、PI3K/Akt、slit-robo信号通路调控DR的RGC凋亡并观察BDNF是否通过miR-212对DR的RGC有保护作用；3.miR-203是否通过靶基因SOCS3和SOCS6分别经JAK/STAT3及PI3K/Akt信号通路调控DR的RGC凋亡。本课题拟从体内外揭示单个miRNA的分子机理，为临床治疗寻找有价值的作用靶点。

中文关键词： 糖尿病视网膜病变；视网膜神经节细胞；细胞凋亡；小干扰RNA

英文摘要： MiRNAs consist of small, noncoding RNAs, inducing translational repression/ degradation of mRNA and attenuating protein translation. Evidence has uncovered the critical role of miRNAs in apoptosis of retinal ganglion cells (RGCs) in diabetic retinopathy (DR). In our preliminary experiment, there is evidence that miR-212 and miR-203 target specific mRNAs for regulating the progression of DR. The functionality of miR-212 and miR-203 lies in its contribution to regulating apoptosis in several diseases. To define the role of miR-212 and miR-203 in apoptosis of RGCs in DR and to understand the molecular mechanism further, we will give an analysis from the following aspects through Dual-luciferase assay system and transgenic technology: first, we will investigate whether miR-212 and miR-203 could regulate apoptosis of RGCs in DR; second, we will investigate whether the expression of target gene p300, slit2 and p300/p53, PI3K/Akt, slit-robo signalling pathway are involved in miR-212's suspension or abrogation of apoptosis in RGCs, meanwhile, we will focus on mechanisms of brain derived neurotrophic factor in DR, which select the upstream signaling pathway regulating the expression of miR-212 as the cut in point; third, we will investigate whether miR-203 could mediate the processe of apoptosis in RGCs by controling the expression of target gene socs3, socs6 and STAT3, PI3K/Akt signalling pathway. This project will illuminate molecular mechanism of miR-212 and miR-203 in the pathogenesis of DR by biological methods and provide experimental evidences for potential value in prevention and treatment of DR.

英文关键词： diabetic retinopathy;retinal ganglion cell;apoptosis;siRNA