miR-34c通过输尿管梗阻减轻上皮-间质转化和肾纤维化。

miR-34c attenuates epithelial-mesenchymal transition and kidney fibrosis with ureteral obstruction.

作者信息

Morizane Ryuji, Fujii Shizuka, Monkawa Toshiaki, Hiratsuka Ken, Yamaguchi Shintaro, Homma Koichiro, Itoh Hiroshi

机构信息

1] Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan [2].

Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.

出版信息

Sci Rep. 2014 Apr 3;4:4578. doi: 10.1038/srep04578.

micro RNAs (miRNAs) are small non-coding RNAs that act as posttranscriptional repressors by binding to the 3'-UTR of target mRNAs. On the other hand, mesenchymal-epithelial transition (EMT) and kidney fibrosis is a pathological process of chronic kidney disease (CKD), and its relationship to miRNAs is becoming recognized as a potential target for CKD therapies. To find new miRNAs involved in EMT, we examined miRNA expression in experimental models of EMT and renal epithelialization using microarray, and found that miR-34c attenuates EMT induced by TGF-β in a mouse tubular cell line. To confirm the effects of miR-34c in vivo, we administered the precursor of miR-34c to mice with unilateral ureteral obstruction, and miR-34c decreased kidney fibrosis area and the expression of connective tissue growth factor, α-SMA, collagen type 1, collagen type 3 and fibronectin. In conclusion, our study showed miR-34c attenuates EMT and kidney fibrosis of mice with ureteral obstruction.

微小RNA（miRNA）是一类小的非编码RNA，通过与靶mRNA的3'-非翻译区（3'-UTR）结合，作为转录后抑制因子发挥作用。另一方面，间充质-上皮转化（EMT）和肾纤维化是慢性肾脏病（CKD）的一个病理过程，其与miRNA的关系正被认为是CKD治疗的一个潜在靶点。为了发现参与EMT的新miRNA，我们使用微阵列检测了EMT和肾上皮化生实验模型中的miRNA表达，发现miR-34c在小鼠肾小管细胞系中减弱了由转化生长因子-β（TGF-β）诱导的EMT。为了在体内证实miR-34c的作用，我们将miR-34c的前体给予单侧输尿管梗阻的小鼠，miR-34c减少了肾纤维化面积以及结缔组织生长因子、α-平滑肌肌动蛋白（α-SMA）、Ⅰ型胶原、Ⅲ型胶原和纤连蛋白的表达。总之，我们的研究表明miR-34c减弱了输尿管梗阻小鼠的EMT和肾纤维化。