MicroRNA21 promotes interstitial fibrosis via targeting DDAH1: a potential role in renal fibrosis.

Scarring of the kidney directly promotes loss of kidney function. A thorough understanding of renal fibrosis at the molecular level is urgently needed. One prominent microRNA, miR-21, was previously reported to be up-regulated in renal fibrosis, but its mechanism is unclear. In the present study, an unbiased search for downstream messenger RNA targets of miR-21 using the HK-2 human tubular epithelial cell line was performed. Effects of the target gene in renal fibrosis and underlying mechanism were explored. Results show that forced expression of miR-21 significantly increased cell apoptosis, interstitial deposition, and decreased E-cadherin level of the HK-2 cells. Conversely, inhibition of miR-21 promoted the opposite effects. We identified that miR-21 directly interacted with the 3'-untranslated region of the suppressor of dimethylarginine dimethylaminohydrolase 1 (DDAH1) by dual-luciferase assay. Moreover, pcDNA3.1-DDAH1 pretreatment could effectively reduce α-SMA, collagen I, fibronectin expression, and promoted E-cadherin expression, as well as inhibiting HK-2 cell apoptosis, while all those effects can be attenuated by pretreatment with the Wnt/ß-catenin signaling activator Licl. Taken together, our results suggest that miR-21 may regulate renal fibrosis by the Wnt pathway via directly targeting DDAH1. Therefore, this study may provide novel strategies for the development of renal fibrosis therapy.