title: Effect of miR-146 targeted HDMCP up-regulation in the pathogenesis of nonalcoholic steatohepatitis.
abstract: OBJECTIVE
  Mitochondrial dysfunction plays an important role inthe pathogenesis of nonalcoholic steatohepatitis (NASH), where uncoupling protein (UCP) is actively involved. We previously reported the uncoupling activity of HDMCP and its role in liver steatosis. We now aim to investigate the degree and therapeutic effect of HDMCP in NASH and the regulatory role of miR-146 on HDMCP.
  
  
  METHODS
  NASH animal model was established by feeding BALB/c mice with MCD diet while L02 cell was cultured with high concentration of fatty acid (HFFA) for 72h to mimic the steatosis and inflammation of NASH in-vitro appearance. The steatosis level was assessed by H-E/oil-red staining and serum/supernatant marker detection. The inflammation activity was evaluated by levels of Hepatic activity index, transwell, apoptosis degree (TUNEL/flow cytometry) and serum/supernatant marker. HDMCP level was detected by western blot and miRNA expression was tested by qRT-PCR. NASH severity change was recorded after RNA interference while the regulatory role of miR-146 on HDMCP was confirmed by dual luciferase report system. The H2O2 and ATP levels were measured for mechanism exploration.
  
  
  RESULTS
  Increased HDMCP expression was identified in NASH animal model and HFFA-72h cultured L02 cell. Moreover, under regulation of miR-146, NASH alleviation was achieved after HDMCP downregulation in both in vivo and in vitro, according to the declination of steatosis and inflammation related markers. Though H2O2 and ATP levels were increased and decreased in NASH models, HDMCP down regulation both increased their levels.
  
  
  CONCLUSIONS
  The miR-146-HDMCP-ATP/H2O2 pathway may provide novel mechanism and treatment option for NASH.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Gastroenterology, Huzhou Central Hospital, Huzhou, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yi-Peng
authors.initials: YP
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Zun
authors.initials: Z
authors.lastname: Xiang
authors.affiliation: Department of infectious disease, Hangzhou first people's hospital, Hangzhou, China.
authors.forename: Jie-Xia
authors.initials: JX
authors.lastname: Ding
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: You-Ming
authors.initials: YM
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D004195:Disease Models, Animal; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics*; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics*; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics* / Q000473:pathology*; D015854:Up-Regulation
chemical_list: C000622184:HDMCP protein, mouse; D035683:MicroRNAs; C534190:Mirn146 microRNA, mouse; D033681:Mitochondrial Membrane Transport Proteins