microRNA-206 promotes skeletal muscle regeneration and delays progression of Duchenne muscular dystrophy in mice

Skeletal muscle injury activates adult myogenic stem cells, known as satellite cells, to initiate proliferation and differentiation to regenerate new muscle fibers. The skeletal muscle-specific microRNA miR-206 is upregulated in satellite cells following muscle injury, but its role in muscle regener...

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Bibliographic Details
Published inThe Journal of clinical investigation Vol. 122; no. 6; pp. 2054 - 2065
Main Authors Liu, Ning, Williams, Andrew H, Maxeiner, Johanna M, Bezprozvannaya, Svetlana, Shelton, John M, Richardson, James A, Bassel-Duby, Rhonda, Olson, Eric N
Format Journal Article
LanguageEnglish
Published United States American Society for Clinical Investigation 01.06.2012
Subjects
Animals
Biomedical research
Cardiotoxins - adverse effects
Cardiotoxins - pharmacology
Cell Differentiation
Development and progression
Disease Models, Animal
Duchenne muscular dystrophy
Female
Genotype & phenotype
Male
Mice
Mice, Knockout
MicroRNA
MicroRNAs
MicroRNAs - genetics
MicroRNAs - metabolism
Muscle Development
Muscle, Skeletal - injuries
Muscle, Skeletal - metabolism
Muscle, Skeletal - pathology
Muscles
Muscular dystrophy
Muscular Dystrophy, Duchenne - genetics
Muscular Dystrophy, Duchenne - metabolism
Muscular Dystrophy, Duchenne - pathology
Musculoskeletal system
Myogenesis
Properties
Regeneration
Risk factors
Satellite Cells, Skeletal Muscle - metabolism
Satellite Cells, Skeletal Muscle - pathology
Stem cells
United States
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Summary:Skeletal muscle injury activates adult myogenic stem cells, known as satellite cells, to initiate proliferation and differentiation to regenerate new muscle fibers. The skeletal muscle-specific microRNA miR-206 is upregulated in satellite cells following muscle injury, but its role in muscle regeneration has not been defined. Here, we show that miR-206 promotes skeletal muscle regeneration in response to injury. Genetic deletion of miR-206 in mice substantially delayed regeneration induced by cardiotoxin injury. Furthermore, loss of miR-206 accelerated and exacerbated the dystrophic phenotype in a mouse model of Duchenne muscular dystrophy. We found that miR-206 acts to promote satellite cell differentiation and fusion into muscle fibers through suppressing a collection of negative regulators of myogenesis. Our findings reveal an essential role for miR-206 in satellite cell differentiation during skeletal muscle regeneration and indicate that miR-206 slows progression of Duchenne muscular dystrophy.
Bibliography:Authorship note: Ning Liu and Andrew H. Williams contributed equally to this work.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI62656