title: MicroRNA-328, a Potential Anti-Fibrotic Target in Cardiac Interstitial Fibrosis.
abstract: OBJECTIVE
  Deregulated myocardial fibrosis is associated with a wide spectrum of cardiac conditions, being considered one of the major causes for heart disease. Our study was designed to investigate the role of microRNA-328 (miR-328) in regulating cardiac fibrosis.
  
  
  METHODS
  We induced cardiac fibrosis following MI by occlusion of the left coronary artery in C57BL/6 mice. Real-time PCR was employed to evaluate the level of miR-328. Masson's Trichrome stain was used to evaluate the development of fibrosis. Luciferase activity assay was performed to confirm the miRNA's binding site in the TGFβRIII gene. Western blot analysis was used to examine TGFβRIII, p-smad2/3 and TGF-β1 at protein level.
  
  
  RESULTS
  In this study, we found that miR-328 was significantly upregulated in the border zone of infarcted myocardium of wild type (WT) mice; TGFβRIII was downregulated whereas TGF-β1 was upregulated along with increased cardiac fibrosis. And miR-328 stimulated TGF-β1 signaling and promoted collagen production in cultured fibroblasts. We further found that the pro-fibrotic effect of miR-328 was mediated by targeting TGFβRIII. Additionally, cardiac fibrosis was significantly reduced in infarcted heart when treated with miR-328 antisense.
  
  
  CONCLUSIONS
  These data suggest that miR-328 is a potent pro-fibrotic miRNA and an important determinant of cardiac fibrosis in diseased heart.
authors: Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, P. R. China.
authors: Weijie
authors: W
authors: Du
authors: Haihai
authors: H
authors: Liang
authors: Xu
authors: X
authors: Gao
authors: Xiaoxue
authors: X
authors: Li
authors: Yue
authors: Y
authors: Zhang
authors: Zhenwei
authors: Z
authors: Pan
authors: Cui
authors: C
authors: Li
authors: Yuying
authors: Y
authors: Wang
authors: Yanxin
authors: Y
authors: Liu
authors: Wei
authors: W
authors: Yuan
authors: Ning
authors: N
authors: Ma
authors: Wenfeng
authors: W
authors: Chu
authors: Hongli
authors: H
authors: Shan
authors: Yanjie
authors: Y
authors: Lu
mesh_terms: D000818:Animals; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D054059:Coronary Occlusion / Q000473:pathology / Q000601:surgery; D003331:Coronary Vessels / Q000473:pathology / Q000601:surgery; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009203:Myocardial Infarction / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D011509:Proteoglycans / Q000235:genetics* / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism
chemical_list: C548169:MIRN328 microRNA, mouse; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; D051899:Smad2 Protein; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; C071736:betaglycan; D003094:Collagen; D008156:Luciferases