Document Detail


Loss of miR-29 in myoblasts contributes to dystrophic muscle pathogenesis.
MedLine Citation:
PMID:  22434133     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
microRNAs (miRNAs) are noncoding RNAs that regulate gene expression in post-transcriptional fashion, and emerging studies support their importance in a multitude of physiological and pathological processes. Here, we describe the regulation and function of miR-29 in Duchenne muscular dystrophy (DMD) and its potential use as therapeutic target. Our results demonstrate that miR-29 expression is downregulated in dystrophic muscles of mdx mice, a model of DMD. Restoration of its expression by intramuscular and intravenous injection improved dystrophy pathology by both promoting regeneration and inhibiting fibrogenesis. Mechanistic studies revealed that loss of miR-29 in muscle precursor cells (myoblasts) promotes their transdifferentiation into myofibroblasts through targeting extracellular molecules including collagens and microfibrillar-associated protein 5 (Mfap5). We further demonstrated that miR-29 is under negative regulation by transforming growth factor-β (TGF-β) signaling. Together, these results not only identify TGF-β-miR-29 as a novel regulatory axis during myoblasts conversion into myofibroblasts which constitutes a novel contributing route to muscle fibrogenesis of DMD but also implicate miR-29 replacement therapy as a promising treatment approach for DMD.
Authors:
Lijun Wang; Liang Zhou; Peiyong Jiang; Leina Lu; Xiaona Chen; Huiyao Lan; Denis C Guttridge; Hao Sun; Huating Wang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-03-20
Journal Detail:
Title:  Molecular therapy : the journal of the American Society of Gene Therapy     Volume:  20     ISSN:  1525-0024     ISO Abbreviation:  Mol. Ther.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-01     Completed Date:  2012-11-07     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  100890581     Medline TA:  Mol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1222-33     Citation Subset:  IM    
Affiliation:
Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation
Cell Transdifferentiation
Cells, Cultured
Down-Regulation / genetics
Extracellular Matrix / genetics
Fibrosis / genetics
Gene Expression Regulation
Mice
Mice, Inbred mdx
MicroRNAs / administration & dosage,  genetics*
Models, Biological
Muscle, Skeletal / metabolism
Muscular Dystrophy, Duchenne / genetics*
Myoblasts / cytology,  metabolism*
Myofibroblasts / cytology
Regeneration
Signal Transduction
Transforming Growth Factor beta / metabolism
Chemical
Reg. No./Substance:
0/MIRN29 microRNA, mouse; 0/MicroRNAs; 0/Transforming Growth Factor beta
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