title: microRNA-29b Mediates the Antifibrotic Effect of Tanshinone IIA in Postinfarct Cardiac Remodeling.
abstract: BACKGROUND
  Tanshinone IIA (TSN) is one of the main components isolated from Danshen, which is widely used for the treatment of cardiovascular diseases. The transforming growth factor beta (TGF-β) signaling pathway and microRNA (miR)-29b play important roles in the progression of cardiac fibrosis and the modulation of cardiac fibroblast (CF) function. Our study investigated the role of miR-29b in the cardioprotective effects of TSN in postinfarct cardiac remodeling.
  
  
  RESULTS
  Echocardiography demonstrated that medium-dose TSN (TSN-M) and high-dose TSN (TSN-H) significantly inhibited postinfarct cardiac fibrosis and improved the impaired left ventricular function in rats subjected to acute myocardial infarction. Moreover, quantitative real-time polymerase chain reaction and Western blot demonstrated that TSN-M and TSN-H downregulated the expression of TGF-β1, Col1a1, Col3a1, and α-SMA but upregulated the expression of miR-29b. CFs treated with TSN showed inhibited TGF-β signaling pathway, downregulated expression of Col1a1, Col3a1, and α-SMA, and upregulated miR-29b expression in vitro. Furthermore, treatment with a miR-29b inhibitor dramatically inhibited these TSN-induced antifibrotic effects, suggesting that miR-29b may be responsible for the antifibrotic effects of TSN. In addition, treatment with Smad3 siRNA significantly inhibited miR-29b expression in CFs, which implies that Smad3 signaling promotes miR-29b expression on CFs.
  
  
  CONCLUSIONS
  TSN exerts antifibrotic effects in postinfarct cardiac fibrosis by upregulating the expression of miR-29b, which is mediated by the TGF-β-Smad3 signaling pathway.
authors: *Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; and †Department of Internal Medicine, Henan Medical College, Zhengzhou, China.
authors: Fan
authors: F
authors: Yang
authors: Ping
authors: P
authors: Li
authors: Haiyu
authors: H
authors: Li
authors: Qiangwei
authors: Q
authors: Shi
authors: Shuaibing
authors: S
authors: Li
authors: Luosha
authors: L
authors: Zhao
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D015854:Up-Regulation; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D045784:Abietanes; C526366:MIRN29 microRNA, rat; D035683:MicroRNAs; D051900:Smad3 Protein; C497787:Smad3 protein, rat; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; C021751:tanshinone; D003094:Collagen