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MicroRNA-24 Regulates Cardiac Fibrosis after Myocardial Infarction.
MedLine Citation:
PMID:  22260784     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Cardiac fibrosis after myocardial infarction (MI) has been identified as a key factor in the development of heart failure. Although dysregulation of miRNAs is involved in various pathophysiologic processes in the heart, the role of miRNA in fibrosis regulation after MI is unclear. Previously we observed the correlation between fibrosis and the miR-24 expression in hypertrophic hearts, here we assessed how miR-24 regulates fibrosis after MI. Using qRT-PCR, we showed that microRNA-24 was down-regulated in the MI heart, the change in miR-24 expression was closely related to extracellular matrix (ECM) remodeling. In vivo, miR-24 could improve heart function and attenuate fibrosis in the infarct border zone of the heart 2 weeks after MI through intramyocardial injection of Lentiviruses. Moreover, in-vitro experiments suggested that up-regulation of miR-24 by synthetic miR-24 precursors could reduce fibrosis and also decrease the differentiation and migration of cardiac fibroblasts(CFs). TGF-β (a pathologic mediator of fibrotic disease) increased miR-24 expression, over-expression of miR-24 reduced TGF-β secretion and Smad2/3 phosphorylation in cardiac fibroblasts. Using microarray analyses and bioinformatics analyses, we found furin to be a potential target for miR-24 in fibrosis (furin is a protease which control latent TGF-β activation processing). Finally, we demonstrated that protein and mRNA levels of furin were regulated by miR-24 in cardiac fibroblasts. These findings suggest that miR-24 has a critical role in cardiac fibroblast function and cardiac fibrosis after MI through a furin-TGF-β pathway. Thus, miR-24 may be used as a target for treatment of MI and other fibrotic heart diseases. © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
Authors:
Jue Wang; Weicong Huang; Ruixia Xu; Yu Nie; Xiaoqing Cao; Jiang Meng; Xiuqing Xu; Shengshou Hu; Zhe Zheng
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-19
Journal Detail:
Title:  Journal of cellular and molecular medicine     Volume:  -     ISSN:  1582-4934     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101083777     Medline TA:  J Cell Mol Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
Affiliation:
State Key Laboratory of Translational Cardiovascular Medicine, Fuwai Hospital & Cardiovascular Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's R China; Department of Surgery, Fuwai Hospital & Cardiovascular Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's R China; Research Center for Cardiac Regenerative Medicine, Ministry of Health, Beijing, People's R China; Department of thoracic and cardiovascular surgery, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, 325000, China.
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