miR-206 modulates the pathogenesis of muscular dystrophy of mdx mice

In response to skeletal muscle injury, adult myogenic stem cells, known as satellite cells, are activated and undergo proliferation and differentiation to regenerate new muscle fibers. The skeletal muscle-specific microRNA, miR-206, is up-regulated in satellite cells following muscle injury, but its role in muscle regeneration has not been defined. Here we show that skeletal muscle regeneration in response to cardiotoxin injury is impaired in mice lacking miR-206. Loss of miR-206 also accelerates and exacerbates the dystrophic phenotype of mdx mice, a model for Duchenne muscular dystrophy. MiR-206 promotes satellite cell differentiation and fusion to form multinucleated myofibers by 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 as a modulator of Duchenne muscular dystrophy. total RNA obtained from TA muscle of mdx and 3 miR-206 KO; mdx mice at 3 months of age.当骨骼肌受到损伤时，被称为卫星细胞（satellite cells）的成体肌源性干细胞会被激活，并通过增殖与分化过程再生新的肌纤维。骨骼肌特异性微小RNA（microRNA）miR-206会在肌肉损伤后的卫星细胞中表达上调，但目前尚未明确其在肌肉再生中的具体作用。本研究证实，缺失miR-206的小鼠在应对心脏毒素（cardiotoxin）损伤时，其骨骼肌再生过程受到显著损伤。miR-206的缺失还会加速并加重mdx小鼠的肌营养不良表型，而mdx小鼠是杜氏肌营养不良症（Duchenne muscular dystrophy, DMD）的经典动物模型。miR-206通过抑制一系列肌发生负调控因子，促进卫星细胞的分化与融合，进而形成多核肌纤维。本研究结果揭示了miR-206在骨骼肌再生过程中对卫星细胞分化的关键调控作用，以及其作为杜氏肌营养不良症调控因子的功能。本研究使用的总RNA提取自3月龄mdx小鼠及3株miR-206敲除（KO）mdx小鼠的胫骨前肌（TA muscle）。