miR-127 enhances myogenic cell differentiation by targeting S1PR3.
miR-127 enhances myogenic cell differentiation by targeting S1PR3.
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miR-127通过靶向S1PR3增强肌原性细胞分化
DOI：
10.1038/cddis.2017.128
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发表时间：
2017-03-30
影响因子：
9
通讯作者：
Zhu D
中科院分区：
文献类型：
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作者：
Zhai L;Wu R;Han W;Zhang Y;Zhu D
MicroRNAs （miRNAs）最近被认为与肌肉干细胞功能有关。已知miR-127主要在骨骼肌中表达，但其在肌源性分化和肌肉再生中的作用尚不清楚。在这里，我们发现miR-127在C2C12和卫星细胞（SC）分化过程中上调，并通过建立稳定表达miR-127的C2C12细胞，证明在C2C12细胞中过表达miR-127可增强肌源性细胞分化。为了研究miR-127在体内肌肉发育和再生中的功能，我们培育了miR-127转基因小鼠。与野生型小鼠相比，这些小鼠通过促进SC分化表现出显著加速的肌肉再生。从机制上讲，我们证明了编码鞘氨醇-1-磷酸受体3 （S1PR3）的基因是miR-127促进肌源性细胞分化的功能所必需的靶标。重要的是，在mdx肌营养不良模型小鼠中过表达miR-127显著改善了疾病表型。因此，我们的研究结果表明，miR-127可能作为治疗人类骨骼肌疾病的潜在治疗靶点。
MicroRNAs (miRNAs) have recently been implicated in muscle stem cell function. miR-127 is known to be predominantly expressed in skeletal muscle, but its roles in myogenic differentiation and muscle regeneration are unknown. Here, we show that miR-127 is upregulated during C2C12 and satellite cell (SC) differentiation and, by establishing C2C12 cells stably expressing miR-127, demonstrate that overexpression of miR-127 in C2C12 cells enhances myogenic cell differentiation. To investigate the function of miR-127 during muscle development and regeneration in vivo, we generated miR-127 transgenic mice. These mice exhibited remarkably accelerated muscle regeneration compared with wild-type mice by promoting SC differentiation. Mechanistically, we demonstrated that the gene encoding sphingosine-1-phosphate receptor 3 (S1PR3), a G-protein-coupled receptor for sphingosine-1-phosphate, is a target of miR-127 required for its function in promoting myogenic cell differentiation. Importantly, overexpression of miR-127 in muscular dystrophy model mdx mice considerably ameliorated the disease phenotype. Thus, our findings suggest that miR-127 may serve as a potential therapeutic target for the treatment of skeletal muscle disease in humans.