title: MicroRNA-370 Attenuates Hepatic Fibrogenesis by Targeting Smoothened.
abstract: OBJECTIVE
  Recent research shows that abnormal expression of microRNA plays an important role in the process of hepatic fibrosis . miR-370 has been reported to be involved in liver function and is suppressed during hepatic carcinogenesis. The aim of this study was to investigate the role of miR-370 in hepatic fibrosis.
  
  
  METHODS
  The expression levels of miR-370 in rat fibrotic livers and activated hepatic stellate cells (HSCs) were evaluated by quantitative real-time PCR. The effect of miR-370 on the activation of HSCs was analyzed by flow cytometric analyses, real-time PCR and Western blot. Adenovirus carrying miR-370 was injected through the tail vein to access the effect of miR-370 on hepatic fibrosis induced by CCl4 in rats. The downstream targets of miR-370 were predicted by the Target Scan database and verified by luciferase assays, real-time PCR and Western blot in HSCs and were further confirmed by immunohistochemistry in vivo.
  
  
  RESULTS
  Real-time PCR showed that miR-370 expression was significantly reduced in rat fibrotic livers and TGFβ1-stimulated HSCs. Overexpression of miR-370 inhibited the proliferation of HSC-T6 cells via inducing cell apoptosis and suppressed the activation of HSCs. Upregulation of miR-370 obviously attenuated the CCl4-induced liver fibrosis in rats. miR-370 was directly bound to the 3'UTR of Smoothened (SMO) and suppressed the expression of SMO in HSCs and fibrotic livers.
  
  
  CONCLUSIONS
  Our study demonstrated that miR-370 plays an inhibitory role in hepatic fibrogenesis by targeting SMO. Restoration of miR-370 may have beneficial effects on the treatment of liver fibrosis.
authors: Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical College of Nantong University, Nantong, 226001, Jiangsu, China.
authors: Cui-Hua
authors: CH
authors: Lu
authors: Qian-Ru
authors: QR
authors: Hou
authors: Long-Fei
authors: LF
authors: Deng
authors: Chen
authors: C
authors: Fei
authors: Wen-Ping
authors: WP
authors: Xu
authors: Qin
authors: Q
authors: Zhang
authors: Kai-Ming
authors: KM
authors: Wu
authors: Bei-Fang
authors: BF
authors: Ning
authors: Wei-Fen
authors: WF
authors: Xie
authors: Xin
authors: X
authors: Zhang
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation; D055166:Hepatic Stellate Cells / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D000072086:Smoothened Receptor; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C526503:MIRN370 microRNA, human; C000600513:MIRN370 microRNA, rat; D035683:MicroRNAs; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; C498555:Smo protein, rat; D000072086:Smoothened Receptor; C000604450:Snai2 protein, rat; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors