microRNA-10a及其组蛋白乙酰化介导糖尿病肾病肾小球系膜损伤机制及花青素的干预效应

项目名称： microRNA-10a及其组蛋白乙酰化介导糖尿病肾病肾小球系膜损伤机制及花青素的干预效应

项目编号： No.31200873

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 生理学与整合生物学

项目作者： 单群

作者单位： 江苏师范大学

项目金额： 23万元

中文摘要： 糖尿病肾病仍缺乏有效治疗手段，理想治疗方法和药物的开发依赖于对糖尿病肾病发生机制的认识。肾小球系膜病变是糖尿病肾病发生和发展关键环节。肾系膜病变很大程度上依赖于膜上受体及胞内信号转导通路的表达改变，而这些改变又依赖于基因的表达调控，但糖尿病肾病的基因调控机制仍不清楚。miRNA是近年发现基因表达调控的一种方式，它参与调节多种生理和病理过程。最近我们利用高通量测序法发现糖尿病肾病下,肾脏miR-10a显著下调，且过表达miR-10a可以改善病症；与糖尿病肾病密切相关的CREB1可能是miR-10a下游靶标,而HDAC3可能是miR-10a表达的上游调节子。应用花青素干预，发现花青素不仅能影响HDAC3活性且能减轻病症。本项目拟高脂/链脲佐菌素诱导糖尿病肾病小鼠为模型，从整体、细胞和分子水平阐明，miR-10a及其组蛋白乙酰化调控糖尿病肾病机制及花青素的干预效应，为研发理想防治药物提供新靶标。

中文关键词： 微小RNA10a；组蛋白乙酰化；糖尿病肾病；肾小球系膜损伤；花青素

英文摘要： The development of new effective therapy techniques and drugs depends on exploring the mechanisms of diabetic nephropathy. Mesangial lesions contribute to the induction and maintenance of diabetic nephropathy. Mesangial lesions mainly depend on the abnormal integration of membrane receptors, ion channels and intracellular signal transduction pathway mediated by modification of diabetic nephropathy-related genes expression. However, the mechanisms of gene modification underlying diabetic nephropathy are still poorly understood. Serveral studies have shown that microRNA as a post-transcriptional regulator may be involved in many physiological and pathological processes including diabetic nephropathy through regulating expression of related genes. Through high-throughput sequencing, we found that microRNA-10a in kidney was decreased significantly in a high fat diet/streptozotocin-induced diabetic nephropathy model. Furthermore, renal parenchyma injection of microRNA-10a mimics could markedly reverse the injury of kidney. Bioinformatic analysis and luciferase assays confirmed that CREB1 gene is one of the target mRNA of microRNA-10a, while HDAC3 is an upstream regulator of microRNA-10a. In addition, we found that purple sweet potato color could affect HDAC3 activity and ameliorated diabetic nephropathy. In this prop

英文关键词： microRNA-10a；histone acetylation；diabetic nephropathy；glomerular mesangial lesion；PSPC