Role of miR-200c in Myogenic Differentiation Impairment via p66Shc: Implication in Skeletal Muscle Regeneration of Dystrophic mdx Mice.
Role of miR-200c in Myogenic Differentiation Impairment via p66Shc: Implication in Skeletal Muscle Regeneration of Dystrophic mdx Mice.
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DOI：
10.1155/2018/4814696
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发表时间：
2018
影响因子：
--
通讯作者：
Magenta A
中科院分区：
文献类型：
--
作者：
D'Agostino M;Torcinaro A;Madaro L;Marchetti L;Sileno S;Beji S;Salis C;Proietti D;Imeneo G;C Capogrossi M;De Santa F;Magenta A
Duchenne型肌营养不良症（DMD）是一种与Dystrophin基因突变相关的遗传性疾病，该基因调节肌纤维的完整性和肌肉变性，其特征在于氧化应激增加。我们先前发表了活性氧（ROS）诱导miR-200 c，这是负责细胞凋亡和衰老。此外，我们证明了miR-200 c增加ROS产生并磷酸化Ser-36中的p66 Shc。p66 Shc在肌肉分化中起着重要作用;我们以前发现，p66 Shc −/−肌肉卫星细胞显示出较低的氧化应激水平和较高的增殖率，并且比野生型（wt）细胞分化得更快。此外，与野生型细胞相比，MyoD过表达诱导的肌原性转化在p66 Shc −/−成纤维细胞中更有效。在此，我们报道了miR-200 c在培养的成肌细胞中的过表达损害骨骼肌分化。此外，其在分化的肌管中的过表达降低了分化指数。此外，抗miR-200 c治疗改善肌原性分化。在保持中，我们发现miR-200 c和p66 Shc Ser-36磷酸化在mdx肌肉中增加。总之，miR-200 c抑制肌肉分化，而其抑制改善分化，并且其表达水平在mdx小鼠和DMD的分化的人成肌细胞中增加。因此，miR-200 c可能是肌肉萎缩和肌管丢失的原因，最有可能是通过病理性疾病如DMD中的p66 Shc依赖性机制。
Duchenne muscular dystrophy (DMD) is a genetic disease associated with mutations of Dystrophin gene that regulate myofiber integrity and muscle degeneration, characterized by oxidative stress increase. We previously published that reactive oxygen species (ROS) induce miR-200c that is responsible for apoptosis and senescence. Moreover, we demonstrated that miR-200c increases ROS production and phosphorylates p66Shc in Ser-36. p66Shc plays an important role in muscle differentiation; we previously showed that p66Shc−/− muscle satellite cells display lower oxidative stress levels and higher proliferation rate and differentiated faster than wild-type (wt) cells. Moreover, myogenic conversion, induced by MyoD overexpression, is more efficient in p66Shc−/− fibroblasts compared to wt cells. Herein, we report that miR-200c overexpression in cultured myoblasts impairs skeletal muscle differentiation. Further, its overexpression in differentiated myotubes decreases differentiation indexes. Moreover, anti-miR-200c treatment ameliorates myogenic differentiation. In keeping, we found that miR-200c and p66Shc Ser-36 phosphorylation increase in mdx muscles. In conclusion, miR-200c inhibits muscle differentiation, whereas its inhibition ameliorates differentiation and its expression levels are increased in mdx mice and in differentiated human myoblasts of DMD. Therefore, miR-200c might be responsible for muscle wasting and myotube loss, most probably via a p66Shc-dependent mechanism in a pathological disease such as DMD.
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影响因子：
17.1
作者：
Biressi S;Miyabara EH;Gopinath SD;Carlig PM;Rando TA
通讯作者：
Rando TA
影响因子：
--
作者：
Magenta A;Greco S;Capogrossi MC;Gaetano C;Martelli F
通讯作者：
Martelli F
影响因子：
6.6
作者：
Carlomosti, Fabrizio;D'Agostino, Marco;Magenta, Alessandra
通讯作者：
Magenta, Alessandra
影响因子：
82.9
作者：
Dumont NA;Wang YX;von Maltzahn J;Pasut A;Bentzinger CF;Brun CE;Rudnicki MA
通讯作者：
Rudnicki MA
影响因子：
4.9
作者：
Mann CJ;Perdiguero E;Kharraz Y;Aguilar S;Pessina P;Serrano AL;Muñoz-Cánoves P
通讯作者：
Muñoz-Cánoves P