标题：Downregulation of microRNA-429 contributes to angiotensin II-induced profibrotic effect in rat kidney
作者：Wang, Zhengchao; Zhu, Qing; Wang, Weili; Hu, Junping; Li, Pin-Lan; Yi, Fan; Li, Ningjun
作者机构：[Wang, Zhengchao; Zhu, Qing; Wang, Weili; Hu, Junping; Li, Pin-Lan; Li, Ningjun] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Med Coll, Virgi 更多
通讯作者地址：[Li, NJ]Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Med Coll, Virginia Campus,POB 980613, Richmond, VA 23298 USA.
来源：AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
关键词：albuminuria; epithelial-to-mesenchymal transition; proximal tubular cell
摘要：MicroRNA (miR) 429 has been shown to inhibit epithelial-to-mesenchymal transition (EMT) in cancer cells. However, the role of miR429 in EMT in non-cancer cells has not been defined, especially in the kidneys. The present study determined whether miR429 participated in angiotensin (ANG) II-induced EMT and fibrogenesis in renal cells. In NRK-52E cells, a rat proximal tubular cell line, incubation of ANG II (10(-9) M) for 24 h significantly reduced the level of miR429 by 60% and increased the protein levels of mesenchymal markers alpha-smooth muscle actin and fibroblast-specific protein-1 by threefold and decreased epithelial marker E-cadherin by 60%, which was blocked by losartan, an AT1 receptor antagonist. Treatment of cells with miR429 inhibitor produced similar changes in the above EMT markers to that induced by ANG II. In cells overexpressed with miR429 transgene, ANG II-induced increases in collagen were abolished. Male Sprague-Dawley rats were infused with ANG II (200 ng.kg(-1).min(-1)) for 12 days, and the levels of miR429 in the kidneys were reduced by 75%. Intrarenal transfection of Ientivirus expressing miR429 also reversed the ANG II-induced changes in the EMT markers and collagen in the kidneys. The ANG II-induced increase in urinary albumin was significantly inhibited by miR429 transgene. There was no difference in the increases of blood pressure between ANG II- and ANG II+miR429 transgene-treated rats. These data suggest that ANG II-induced inhibition of miR429 contributes to ANG II-induced transdifferentiation and fibrogenesis in renal cells and that miR429 protects against ANG II-induced kidney damages.