title: MiR-22 may Suppress Fibrogenesis by Targeting TGFβR I in Cardiac Fibroblasts.
abstract: OBJECTIVE
  Cardiac fibrosis after myocardial infarction (MI) has been identified as a key factor in the development of heart failure, but the mechanisms undelying cardiac fibrosis remained unknown. microRNAs (miRNAs) are novel mechanisms leading to fibrotic diseases, including cardiac fibrosis. Previous studies revealed that miR-22 might be a potential target. However, the roles and mechanisms of miR-22 in cardiac fibrosis remained ill defined. The present study thus addressed the impact of miR-22 in cardiac fibrosis.
  
  
  METHODS
  After seven days following coronary artery occlusion in mice, tissues used for histology were collected and processed for Masson's Trichrome staining. In addition, cardiac fibroblasts were transfected with mimics and inhibitors of miR-22 using Lipofectamin 2000, and luciferase activity was measured in cell lysates using a luciferase assay kit. Western blotting was used to detect the expression of collagen1, α-SMA and TGFβRI proteins levels, and real time-PCR was employed to measure the Col1α1, Col3α1, miR-22 and TGFβRI mRNA levels.
  
  
  RESULTS
  In this study, we found that miR-22 was dynamically downregulated following MI induced by permanent ligation of the left anterior descending coronary artery for 7 days, an effect paralleled by significant collagen deposition. Inhibition of miR-22 with AMO-22 resulted in increased expression of Col1α1, Col3α1 and fibrogenesis in cultured cardiac fibroblasts. Conversely, overexpression of miR-22 in cultured cardiac fibroblasts significantly abrogated angiotensin II-induced collagen formation and fibrogenesis. Furthermore, we found that TGFβRI is a direct target for miR-22, and downregulation of TGFβR may have mediated the antifibrotic effect of miR-22.
  
  
  CONCLUSIONS
  Our data clearly demonstrate that miR-22 acts as a novel negative regulator of angiotensin II-induced cardiac fibrosis by suppressing the expression of TGFβRI in the heart and may represent a new potential therapeutic target for treating cardiac fibrosis.
authors.affiliation: Department of Pharmacy, Affiliated Wuxi Children's Hospital, Nanjing Medical University, Wuxi, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Hong
authors.forename: Huaming
authors.initials: H
authors.lastname: Cao
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Jianlin
authors.initials: J
authors.lastname: Ye
authors.forename: Lijun
authors.initials: L
authors.lastname: Sui
authors.forename: Jinhua
authors.initials: J
authors.lastname: Feng
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Cai
authors.forename: Huizhu
authors.initials: H
authors.lastname: Song
authors.forename: Xiuhong
authors.initials: X
authors.lastname: Zhang
authors.forename: Xichuang
authors.initials: X
authors.lastname: Chen
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology*; D005355:Fibrosis; D020868:Gene Silencing / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009203:Myocardial Infarction / Q000235:genetics / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism
chemical_list: C580892:MIRN22 microRNA, rat; D035683:MicroRNAs; C574876:Mirn22 microRNA, mouse; D018125:Receptors, Transforming Growth Factor beta; D000804:Angiotensin II; D003094:Collagen; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625843:Tgfbr1 protein, rat