肾小球系膜病变是糖尿病肾病(DN)最突出的早期改变，PI3K/PTEN信号途径异常与其发生发展关系密切。但由于其调控是多层次的复杂网络，单一PI3K途径尚不能很好解释DN的分子机制。我们的目标是以肾脏特异性microRNA为切入点，从小分子RNA层面上探寻DN中microRNA对PI3K/PTEN信号途径调控机制。方法是首先在前期通过芯片结合生物信息学技术初筛出一个早期DN相关的以PTEN基因为靶点的miRNA－miR-21基础上，构建真核表达载体，检测miR-21在高低糖培养的小鼠肾小球系膜细胞和微量白蛋白尿期db/db小鼠肾脏的表达水平，及与PI3K/PTEN途径在DN中的作用机制，对微量白蛋白尿期db/db小鼠糖、脂、胰岛素分泌及体重等影响，体内外实验发现miR-21可能通过特异性靶向调控PTEN/PI3K信号传导途径，抑制肾小球系膜细胞增殖，延缓db/db蛋白尿，可能是一个新的糖尿病肾病的保护因子。

Diabetic nephropathy (DN) is characterized early in its course by glomerular hypertrophy and, importantly, mesangial hypertrophy, which is associated with the eventual glomerulosclerosis。Despite the great progresses that have been made in recent decades, the mechanism involved in mesangial hypertrophy is not fully understood. We focus on kidney-specific microRNAs to study the regulatory mechanism of DN. On the base of the previous work, miR-21 was one of the DN related kidney specific microRNAs by miRNA array and real-time RT-PCR, We found that miR-21 expression was downregulated in response to early DN in vitro and in vivo. Over-expression of miR-21 inhibited proliferation of mesangial cells and decreased the 24-h urine albumin excretion rate in diabetic db/db mice. Moreover, we identified PTEN as a target of miR-21. We also found PI3K and p-Akt increased in miR-21 treated mesangial cells and db/db mice. Overall, these studies for the first time provide evidence for the potential role of miR-21 in early DN, implying that it might be a novel potential target for intervention and prevention of DN.

肾小球系膜病变是糖尿病肾病(DN)最突出的早期改变，PI3K/PTEN信号途径异常与其发生发展关系密切。但由于其调控是多层次的复杂网络，单一PI3K途径尚不能很好解释DN的分子机制。我们的目标是以肾脏特异性microRNA为切入点，从小分子RNA层面上探寻DN中microRNA对PI3K/PTEN信号途径调控机制。方法是首先在前期通过芯片结合生物信息学技术初筛出一个早期DN相关的以PTEN基因为靶点的miRNA－miR-21基础上，构建真核表达载体，检测miR-21在高低糖培养的小鼠肾小球系膜细胞和微量白蛋白尿期db/db小鼠肾脏的表达水平，及与PI3K/PTEN途径在DN中的作用机制，对微量白蛋白尿期db/db小鼠糖、脂、胰岛素分泌及体重等影响，体内外实验发现miR-21可能通过特异性靶向调控PTEN/PI3K信号传导途径，抑制肾小球系膜细胞增殖，延缓db/db蛋白尿，可能是一个新的糖尿病肾病的保护因子。