title: MicroRNA-101a inhibits cardiac fibrosis induced by hypoxia via targeting TGFβRI on cardiac fibroblasts.
abstract: OBJECTIVE
  Hypoxia is a basic pathological challenge that is associated with numerous cardiovascular disorders including aberrant cardiac remodeling. Transforming growth factor beta (TGF-β) signaling pathway plays a pivotal role in mediating cardiac fibroblast (CF) function and cardiac fibrosis. Recent data suggested that microRNA-101a (miR-101a) exerted anti-fibrotic effects in post-infarct cardiac remodeling and improved cardiac function. This study aimed to investigate the potential relationship between hypoxia, miR-101a and TGF-β signaling pathway in CFs.
  
  
  RESULTS
  Two weeks following coronary artery occlusion in rats, the expression levels of both TGFβ1 and TGFβRI were increased, but the expression of miR-101a was decreased at the site of the infarct and along its border. Cultured rat neonatal CFs treated with hypoxia were characterized by the up-regulation of TGFβ1 and TGFβRI and the down-regulation of miR-101a. Delivery of miR-101a mimics significantly suppressed the expression of TGFβRI and p-Smad 3, CF differentiation and collagen content of CFs. These anti-fibrotic effects were abrogated by co-transfection with AMO-miR-101a, an antisense inhibitor of miR-101a. The repression of TGFβRI, a target of miR-101a, was validated by luciferase reporter assays targeting the 3'UTR of TGFβRI. Additionally, we found that overexpression of miR-101a reversed the improved migration ability of CFs and further reduced CF proliferation caused by hypoxia.
  
  
  CONCLUSIONS
  Our study illustrates that miR-101a exerts anti-fibrotic effects by targeting TGFβRI, suggesting that miR-101a plays a multi-faceted role in modulating TGF-β signaling pathway and cardiac fibrosis.
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Kejing
authors.initials: K
authors.lastname: Wang
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Liao
authors.forename: Qiutang
authors.initials: Q
authors.lastname: Zeng
authors.forename: Yushu
authors.initials: Y
authors.lastname: Li
authors.forename: Fen
authors.initials: F
authors.lastname: Hu
authors.forename: Yuzhou
authors.initials: Y
authors.lastname: Liu
authors.forename: Kai
authors.initials: K
authors.lastname: Meng
authors.forename: Cheng
authors.initials: C
authors.lastname: Qian
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Hongquan
authors.initials: H
authors.lastname: Guan
authors.forename: Kaige
authors.initials: K
authors.lastname: Feng
authors.forename: You
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yimei
authors.initials: Y
authors.lastname: Du
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005355:Fibrosis / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000166:cytology / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D018125:Receptors, Transforming Growth Factor beta; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D053773:Transforming Growth Factor beta1; D003094:Collagen; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625843:Tgfbr1 protein, rat