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

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• 作者：Xiu-Juan Liu ; Quan Hong ; Zhen Wang ; Yan-yan Yu…
• 关键词：MiR ; 21 ; DDAH1 ; Interstitial deposition ; Renal fibrosis ; Wnt/β ; catenin
• 刊名：Molecular and Cellular Biochemistry
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：411
• 期：1-2
• 页码：181-189
• 全文大小：3,027 KB
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• 作者单位：Xiu-Juan Liu (1)
  Quan Hong (2)
  Zhen Wang (1)
  Yan-yan Yu (1)
  Xin Zou (1)
  Li-hong Xu (1)
  
  1. 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
  2. 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
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Biochemistry
  Medical Biochemistry
  Oncology
  Cardiology
  
• 出版者：Springer Netherlands
• ISSN：1573-4919

文摘

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. Keywords MiR-21 DDAH1 Interstitial deposition Renal fibrosis Wnt/β-catenin