title: MicroRNA-34a regulates cardiac fibrosis after myocardial infarction by targeting Smad4.
abstract: BACKGROUND
  Although few microRNAs (miRNAs) have been involved in the regulation of post-ischemic cardiac fibrosis, the exact effect and underlying mechanism of miRNAs in cardiac fibrosis remains unclear. Here, we sought to investigate whether microRNA-34 (miR-34) plays a role in the pathogenic development of myocardial fibrosis.
  
  
  METHODS
  The myocardial infarction (MI) mice model was induced and cardiac fibroblasts were cultured. Histological analyses, quantitative real-time polymerase chain reaction and Western blotting analysis were used.
  
  
  RESULTS
  We found that the miR-34 cluster, especially miR-34a, was upregulated in the MI heart. In vivo, inhibition of miR-34a reduces the severity of experimental cardiac fibrosis in mice. TGF-β1 increased miR-34a expression in cardiac fibroblasts. Overexpressing miR-34a levels increased the profibrogenic activity of TGF-β1 in cardiac fibroblast, whereas inhibition miR-34a levels weakened the activity. Finally, we showed that miR-34a's underlying mechanism during cardiac fibrosis occurs through the targeting of Smad4 expression.
  
  
  CONCLUSIONS
  Our findings provide evidence that miR-34a plays a critical role in the progression of cardiac tissue fibrosis by directly targeting Smad4, which suggests that miR-34a may be new marker for cardiac fibrosis progression and that inhibition of miR-34a may be a promising strategy in the treatment of cardiac fibrosis.
authors.affiliation: Pu Dong New Area People's Hospital, Department of Cardiology , Huan-Nan Road 490#, Shanghai, 201200 , China +86 021 50331692 ; +86 021 50331692 ; daifu_zhang001@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Qi
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Du
authors.forename: Dai-fu
authors.initials: DF
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods; D005355:Fibrosis; D018390:Gene Targeting / Q000379:methods; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000502:physiology*; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D009843:Oligoribonucleotides / Q000008:administration & dosage; D051901:Smad4 Protein / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
chemical_list: C551848:MIRN34a microRNA, mouse; D035683:MicroRNAs; D009843:Oligoribonucleotides; D051901:Smad4 Protein; C490810:Smad4 protein, mouse
keywords: Smad4; TGF-β1; cardiac fibrosis; fibroblasts; microRNA-34a