microRNA-206 promotes skeletal muscle regeneration and delays progression of Duchenne muscular dystrophy in mice
Ning Liu, Andrew H. Williams, Johanna M. Maxeiner, Svetlana Bezprozvannaya, John M. Shelton, James A. Richardson, Rhonda Bassel-Duby, Eric N. Olson
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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Research Article Muscle biology

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

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.