MyoD regulates apoptosis of myoblasts through microRNA-mediated down-regulation of Pax3.
MyoD regulates apoptosis of myoblasts through microRNA-mediated down-regulation of Pax3.
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DOI：
10.1083/jcb.201006025
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发表时间：
2010-10-18
期刊：
影响因子：
--
通讯作者：
Asakura A
中科院分区：
文献类型：
--
作者：
Hirai H;Verma M;Watanabe S;Tastad C;Asakura Y;Asakura A
肌源性转录因子MyoD的抑制是肌肉干细胞维持所必需的。调节细胞凋亡级联反应的分子也参与了骨骼肌的分化和合体融合。MyoD是一种肌源性转录因子，在肌肉分化中发挥重要作用。我们注意到，MyoD−/−成肌细胞通过下调miR-1(microRNA-1)和miR-206以及上调Pax3而表现出显著的抗凋亡作用。这导致了抗凋亡因子Bcl2和Bclxl的转录激活。强迫MyoD表达诱导MyoD−/−成肌细胞miR-1和miR-206表达上调，Pax3、Bcl一2和Bclxl表达下调，细胞凋亡率增加。相反，MyoD基因敲除提高了野生型成肌细胞的细胞存活率。Pax3mRNA的3‘非翻译区包含两个保守的miR-1/miR-206结合位点，这是靶向这些microRNAs(MiRNAs)所必需的。因此，这些数据表明，MyoD不仅通过miRNA下调Pax3的表达来调节终末分化，而且还通过下调Pax3来调节细胞凋亡。最后，MyoD、miR-1和miR-206都在静止的卫星细胞中下调，这可能是维持肌肉干细胞所必需的。
Suppression of the myogenic transcription factor MyoD is required for maintenance of muscle stem cells. The molecules that regulate the apoptosis cascade are also involved in differentiation and syncytial fusion in skeletal muscle. MyoD is a myogenic transcription factor that plays essential roles in muscle differentiation. We noticed that MyoD−/− myoblasts display remarkable resistance to apoptosis by down-regulation of miR-1 (microRNA-1) and miR-206 and by up-regulation of Pax3. This resulted in transcriptional activation of antiapoptotic factors Bcl-2 and Bcl-xL. Forced MyoD expression induces up-regulation of miR-1 and miR-206 and down-regulation of Pax3, Bcl-2, and Bcl-xL along with increased apoptosis in MyoD−/− myoblasts. In contrast, MyoD gene knockdown increases cell survival of wild-type myoblasts. The 3′ untranslated region of Pax3 mRNA contains two conserved miR-1/miR-206–binding sites, which are required for targeting of these microRNAs (miRNAs). Therefore, these data suggest that MyoD not only regulates terminal differentiation but also apoptosis through miRNA-mediated down-regulation of Pax3. Finally, MyoD, miR-1, and miR-206 are all down-regulated in quiescent satellite cells, which may be required for maintenance of muscle stem cells.
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影响因子：
7.8
作者：
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