miR-21对糖尿病肾小管上皮细胞SnoN蛋白表达的调控作用及其机制研究

项目名称： miR-21对糖尿病肾小管上皮细胞SnoN蛋白表达的调控作用及其机制研究

项目编号： No.81460144

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 刘丽荣

作者单位： 贵州医科大学

项目金额： 47万元

中文摘要： 糖尿病肾病（DN）发病率逐年增高，随病情进展发生肾纤维化，发病机制复杂，缺乏有效治疗措施。我们前期发现，DN肾小管上皮细胞（RETC）SnoN蛋白减少可能是致肾纤维化的重要机制，且SnoN表达减少发生于转录后，但其调控机制尚未明确；我们亦发现DN发病过程中RETC的miR-21显著增高，而生物信息学分析显示SnoN是miR-21的候选靶基因，故推测RETC中miR-21增多可能与SnoN蛋白减少有关，然而SnoN与miR-21之间的关系尚未见研究报道。本研究拟以糖尿病大鼠和高糖培养的RETC为研究对象，采用分子生物学等方法，动态观察SnoN和miR-21表达变化、上调或下调RETC中miR-21后对SnoN蛋白表达的影响，用双荧光素酶报告基因法验证SnoN是否为miR-21的靶基因。从体内和体外水平探讨miR-21对糖尿病RETC中SnoN表达的调控作用及其分子机制，为DN防治提供新思路。

中文关键词： 糖尿病肾病；肾小管间质纤维化；核转录共抑制因子SnoN；miR-21

英文摘要： The incidence of diabetic nephropathy (DN) continues to rise. The main pathology of DN is characteristic of renal tubular fibrosis. There is no effective methods to treat DN up to now. SnoN is an important negative regulator of TGF-β1/Smad signaling pathways that plays a key role in the organ fibrosis . MiR-21 can promote the renal fibrosis and bioinformatic analysis show SnoN is its potential target gene. Our recent studies have shown that SnoN protein level reduced and mirR-21 level rised in renal tubular epithelial cells(RTECs) which may be an important mechanism of renal fibrosis in DN and that SnoN expression change occurred at post-transcription level.But we did not know the relationship between SnoN and miR-21 through consulting relevant literatures. Therefore we presume that the SnoN protein reduction in DN is related to miR-21. We intend to employ diabetes mellitus rats model and RETCs under the condition of high concentrations glucose as the research object and to use the methods such as molecular biology, which enhance or inhibit the miR -21 expression level in RETCs.Then we observe cell phenotype and SnoN mRNA and SnoN protein change in RETCs under the condition of high glucose. Later ,we use dual luciferase report gene method to test whether SnoN is the target gene of miR -21.We will discuss the promoting effect of miR -21 on renal fibrosis of DN and its regulatory function of SnoN expression and the molecular mechanism ，so as to offer evidences seeking novel targets and methods for the effective prevention and treatment of DN.

英文关键词： diabetic nephropathy;renal tubular fibrosis;SnoN;miR-21