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microRNA-206 promotes skeletal muscle regeneration and delays progression of Duchenne muscular dystrophy in mice
Ning Liu, … , Rhonda Bassel-Duby, Eric N. Olson
Ning Liu, … , Rhonda Bassel-Duby, Eric N. Olson
Published May 1, 2012
Citation Information: J Clin Invest. 2012;122(6):2054-2065. https://doi.org/10.1172/JCI62656.
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Research Article Muscle biology

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

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Abstract

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.

Authors

Ning Liu, Andrew H. Williams, Johanna M. Maxeiner, Svetlana Bezprozvannaya, John M. Shelton, James A. Richardson, Rhonda Bassel-Duby, Eric N. Olson

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Figure 1

miR-206 is upregulated during skeletal muscle regeneration and in mdx mice.

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miR-206 is upregulated during skeletal muscle regeneration and in mdx mi...
(A) Real-time RT-PCR shows upregulated miRNAs in TA muscle 7 days after CTX injury. y axis represents miRNA expression in injured muscle (CTX) relative to control muscle. n = 6 for each group. (B) Northern blot for miR-206 in control (–) and CTX-injured (+) TA muscle on day 7 after injury. U6 is a loading control. (C) Real-time RT-PCR of miR-1 and miR-206 expression in TA muscle from day 2 to day 30 after CTX injury. (D) Northern blot of miR-206, miR-1, miR-133a, and U6 in various muscles of WT and mdx mice at 3 months of age. GP, gastrocnemius and plantaris; EDL, extensor digitorum longus. Data are presented as mean ± SEM.

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