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

被引:278
|
作者
Liu, Ning [1 ]
Williams, Andrew H. [1 ]
Maxeiner, Johanna M. [1 ]
Bezprozvannaya, Svetlana [1 ]
Shelton, John M. [2 ]
Richardson, James A. [1 ,3 ]
Bassel-Duby, Rhonda [1 ]
Olson, Eric N. [1 ]
机构
[1] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA
[2] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA
[3] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA
来源
JOURNAL OF CLINICAL INVESTIGATION | 2012年 / 122卷 / 06期
关键词
STEM-CELL FUNCTION; SATELLITE CELLS; SELF-RENEWAL; DEFICIENT MICE; DIFFERENTIATION; EXPRESSION; MODEL; PROLIFERATION; HETEROGENEITY; MATURATION;
D O I
10.1172/JCI62656
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:2054 / 2065
页数:12
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