肾脏是衰老最快的器官之一，随着肾脏衰老进展尿液外泌体内物质也发生改变，但尿液外泌体中miRNAs与肾脏衰老之间关系却不明确。申请人前期研究结果提示尿液外泌体中miR-214与肾脏衰老有关。通过生物信息学预测和预实验，申请人提出外泌体中miR-214负调控Pten等下游靶基因引起肾脏衰老。本课题体外实验方面将在细胞系中分析外泌体中miR-214对肾小管上皮细胞功能影响并明确miR-214与PI3K/AKT信号通路之间的关系；体内实验方面利用肾脏衰老大鼠模型明确miR-214对肾脏纤维化的影响以及PI3K/Akt通路在其中起到的作用。最终阐明尿液外泌体中miR-214影响肾脏衰老的作用机制以及miR-214与PI3K/Akt在肾脏衰老过程中的分子机制，为尿外泌体中miRNAs对肾脏衰老的作用研究奠定基础。

Kidney is one of the fastest aging organs. With renal aging, urine exosomes are changing. But it is not clear about the renal aging and microRNA in urine exosomes. The applicant previous studies suggest miR-214 in urine exosome is associated with kidney aging. Through the bioinformatics prediction and forecast experiment, the applicant proposes that miR-214 could negatively regulate target genes (such as Pten) to cause renal aging. For this project, in vitro, we will use renal tubular cell line to study the mechanism of miR-214 in urine exosome and its target genes in PI3K/Akt signal pathway to renal fibrosis; in vivo, the renal aging rat model is using to find the function of miR-214 and PI3K/Akt pathway to renal fibrosis. It will lay the foundation of the study of renal aging.