Document Detail


miR-26a is required for skeletal muscle differentiation and regeneration in mice.
MedLine Citation:
PMID:  23028144     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Multiple microRNAs are known to be induced during the differentiation of myoblasts to myotubes. Yet, experiments in animals have not provided clear evidence for the requirement of most of these microRNAs in myogenic differentiation in vivo. miR-26a is induced during skeletal muscle differentiation and is predicted to target a well-known inhibitor of differentiation, the transforming growth factor β/bone morphogenetic protein (TGF-β/BMP) signaling pathway. Here we show that exogenous miR-26a promotes differentiation of myoblasts, while inhibition of miR-26a by antisense oligonucleotides or by Tough-Decoys delays differentiation. miR-26a targets the transcription factors Smad1 and Smad4, critical for the TGF-β/BMP pathway, and expression of microRNA-resistant forms of these transcription factors inhibits differentiation. Injection of antagomirs specific to miR-26a into neonatal mice derepressed both Smad expression and activity and consequently inhibited skeletal muscle differentiation. In addition, miR-26a is induced during skeletal muscle regeneration after injury. Inhibiting miR-26a in the tibialis anterior muscles through the injection of adeno-associated virus expressing a Tough-Decoy targeting miR-26a prevents Smad down-regulation and delays regeneration. These findings provide evidence for the requirement of miR-26a for skeletal muscle differentiation and regeneration in vivo.
Authors:
Bijan K Dey; Jeffrey Gagan; Zhen Yan; Anindya Dutta
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Genes & development     Volume:  26     ISSN:  1549-5477     ISO Abbreviation:  Genes Dev.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-02     Completed Date:  2012-12-05     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  8711660     Medline TA:  Genes Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2180-91     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
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MeSH Terms
Descriptor/Qualifier:
3' Untranslated Regions / genetics
Animals
Cell Differentiation / genetics*
Cell Line
Cell Proliferation
Gene Expression Regulation, Developmental
Gene Knockdown Techniques
Mice
MicroRNAs / antagonists & inhibitors,  genetics,  metabolism*
Muscle, Skeletal / cytology*,  metabolism,  physiology*
Myoblasts / cytology,  metabolism
Oligoribonucleotides, Antisense / genetics,  metabolism
PAX7 Transcription Factor / metabolism
Regeneration / genetics*
Transcription Factors / metabolism
Up-Regulation
Grant Support
ID/Acronym/Agency:
R01 AR050429/AR/NIAMS NIH HHS; R01 AR053948/AR/NIAMS NIH HHS; R01 AR053948/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/3' Untranslated Regions; 0/MicroRNAs; 0/Mirn26 microRNA, mouse; 0/Oligoribonucleotides, Antisense; 0/PAX7 Transcription Factor; 0/Pax7 protein, mouse; 0/Transcription Factors
Comments/Corrections

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