title: MicroRNA21 promotes interstitial fibrosis via targeting DDAH1: a potential role in renal fibrosis.
abstract: 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/β-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.
authors.affiliation: Department of Nephrology, the 94th Hospital of Chinese People's Liberation Army, Changcheng Hospital affiliated to Nanchang University, Jinggangshan Road 1028, Nanchang, 330002, Jiangxi, People's Republic of China. xiujuan_liu796@163.com.
authors.forename: Xiu-Juan
authors.initials: XJ
authors.lastname: Liu
authors.affiliation: Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, 100039, People's Republic of China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Hong
authors.affiliation: Department of Nephrology, the 94th Hospital of Chinese People's Liberation Army, Changcheng Hospital affiliated to Nanchang University, Jinggangshan Road 1028, Nanchang, 330002, Jiangxi, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Nephrology, the 94th Hospital of Chinese People's Liberation Army, Changcheng Hospital affiliated to Nanchang University, Jinggangshan Road 1028, Nanchang, 330002, Jiangxi, People's Republic of China.
authors.forename: Yan-yan
authors.initials: YY
authors.lastname: Yu
authors.affiliation: Department of Nephrology, the 94th Hospital of Chinese People's Liberation Army, Changcheng Hospital affiliated to Nanchang University, Jinggangshan Road 1028, Nanchang, 330002, Jiangxi, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zou
authors.affiliation: Department of Nephrology, the 94th Hospital of Chinese People's Liberation Army, Changcheng Hospital affiliated to Nanchang University, Jinggangshan Road 1028, Nanchang, 330002, Jiangxi, People's Republic of China.
authors.forename: Li-hong
authors.initials: LH
authors.lastname: Xu
mesh_terms: D020413:3' Untranslated Regions; D000581:Amidohydrolases / Q000235:genetics*; D017209:Apoptosis; D002460:Cell Line; D005355:Fibrosis; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000502:physiology*
chemical_list: D020413:3' Untranslated Regions; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D000581:Amidohydrolases; C059999:dimethylargininase
keywords: DDAH1; Interstitial deposition; MiR-21; Renal fibrosis; Wnt/β-catenin