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
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
相关论文
共 53 条
  • [1] THE VALUE OF MAMMALIAN MODELS FOR DUCHENNE MUSCULAR DYSTROPHY IN DEVELOPING THERAPEUTIC STRATEGIES
    Banks, Glen B.
    Chamberlain, Jeffrey S.
    [J]. MOUSE MODELS OF DEVELOPMENTAL GENETIC DISEASE, 2008, 84 : 431 - 453
  • [2] MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004)
    Bartel, David P.
    [J]. CELL, 2007, 131 (04) : 11 - 29
  • [3] Numb regulates Notch1, but not Notch3, during myogenesis
    Beres, Brian J.
    George, Rajani
    Lougher, Eric J.
    Barton, Michael
    Verrelli, Brian C.
    McGlade, C. Jane
    Rawls, J. Alan
    Wilson-Rawls, Jeanne
    [J]. MECHANISMS OF DEVELOPMENT, 2011, 128 (5-6) : 247 - 257
  • [4] MicroRNAs Involved in Molecular Circuitries Relevant for the Duchenne Muscular Dystrophy Pathogenesis Are Controlled by the Dystrophin/nNOS Pathway
    Cacchiarelli, Davide
    Martone, Julie
    Girardi, Erika
    Cesana, Marcella
    Incitti, Tania
    Morlando, Mariangela
    Nicoletti, Carmine
    Santini, Tiziana
    Sthandier, Olga
    Barberi, Laura
    Auricchio, Alberto
    Musaro, Antonio
    Bozzoni, Irene
    [J]. CELL METABOLISM, 2010, 12 (04) : 341 - 351
  • [5] A Long Noncoding RNA Controls Muscle Differentiation by Functioning as a Competing Endogenous RNA
    Cesana, Marcella
    Cacchiarelli, Davide
    Legnini, Ivano
    Santini, Tiziana
    Sthandier, Olga
    Chinappi, Mauro
    Tramontano, Anna
    Bozzoni, Irene
    [J]. CELL, 2011, 147 (02) : 358 - 369
  • [6] EXPRESSION OF THE MURINE DUCHENNE MUSCULAR-DYSTROPHY GENE IN MUSCLE AND BRAIN
    CHAMBERLAIN, JS
    PEARLMAN, JA
    MUZNY, DM
    GIBBS, RA
    RANIER, JE
    REEVES, AA
    CASKEY, CT
    [J]. SCIENCE, 1988, 239 (4846) : 1416 - 1418
  • [7] A Human-Specific Deletion in Mouse Cmah Increases Disease Severity in the mdx Model of Duchenne Muscular Dystrophy
    Chandrasekharan, Kumaran
    Yoon, Jung Hae
    Xu, Ying
    deVries, Sarah
    Camboni, Marybeth
    Janssen, Paulus M. L.
    Varki, Ajit
    Martin, Paul T.
    [J]. SCIENCE TRANSLATIONAL MEDICINE, 2010, 2 (42)
  • [8] Cellular and molecular regulation of muscle regeneration
    Chargé, SBP
    Rudnicki, MA
    [J]. PHYSIOLOGICAL REVIEWS, 2004, 84 (01) : 209 - 238
  • [9] microRNA-1 and microRNA-206 regulate skeletal muscle satellite cell proliferation and differentiation by repressing Pax7
    Chen, Jian-Fu
    Tao, Yazhong
    Li, Juan
    Deng, Zhongliang
    Yan, Zhen
    Xiao, Xiao
    Wang, Da-Zhi
    [J]. JOURNAL OF CELL BIOLOGY, 2010, 190 (05) : 867 - 879
  • [10] Partitioning of IGFBP-5 actions in myogenesis: IGF-independent anti-apoptotic function
    Cobb, LJ
    Salih, DAM
    Gonzalez, I
    Tripathi, G
    Carter, EJ
    Lovett, F
    Holding, C
    Pell, JM
    [J]. JOURNAL OF CELL SCIENCE, 2004, 117 (09) : 1737 - 1746