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首页> 外文期刊>American Journal of Physiology >Myostatin-induced inhibition of the long noncoding RNA malat1 is associated with decreased myogenesis
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Myostatin-induced inhibition of the long noncoding RNA malat1 is associated with decreased myogenesis

机译：肌生成抑制素诱导的长非编码RNA malat1的抑制与肌发生力降低相关

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Myostatin, a member of the transforming growth factor-β (TGF-β) superfamily of secreted proteins, is a potent negative regulator of myogenesis. Free myostatin induces the phosphorylation of the Smad family of transcription factors, which, in turn, regulates gene expression, via the canonical TGF-β signaling pathway. There is, however, emerging evidence that myostatin can regulate gene expression independent of Smad signaling. As such, we acquired global gene expression data from the gastrocnemius muscle of C57BL/6 mice following a 6-day treatment with recombinant myostatin compared with vehicle-treated animals. Of the many differentially expressed genes, the myostatin-associated decrease (-11.20-fold; P 0.05) in the noncoding metastasis-associated lung adenocarcinoma transcript 1 (Malat1) was the most significant and the most intriguing because of numerous reports describing its novel role in regulating cell growth. We therefore sought to further characterize the role of Malat1 expression in skeletal muscle myogenesis. RT-PCR-based quantification of C2C12 and primary human skeletal muscle cells revealed a significant and persistent upregulation (4-to 7-fold; P 0.05) of Malat1 mRNA during the differentiation of myoblasts into myotubes. Conversely, targeted knockdown of Malat1 using siRNA suppressed myoblast proliferation by arresting cell growth in the G0/G1 phase. These results reveal Malat1 as novel downstream target of myostatin with a considerable ability to regulate myogenesis. The identification of new targets of myostatin will have important repercussions for regenerative biology through inhibition and/or reversal of muscle atrophy and wasting diseases.
机译：肌生长抑制素是分泌蛋白的转化生长因子-β（TGF-β）超家族的成员，是肌发生的有效负调节剂。游离肌生长抑制素诱导转录因子Smad家族的磷酸化，进而通过典型的TGF-β信号传导途径调节基因表达。但是，越来越多的证据表明，肌生成抑制素可以独立于Smad信号传导而调控基因表达。因此，与载体治疗的动物相比，重组肌生长抑制素治疗6天后，我们从C57BL / 6小鼠的腓肠肌中获得了全球基因表达数据。在许多差异表达的基因中，与非编码转移相关的肺腺癌转录本1（Malat1）中与肌肉生长抑制素相关的减少（-11.20倍; P <0.05）是最重要和最引人入胜的，因为有许多报道描述了该基因的新颖性在调节细胞生长中的作用。因此，我们试图进一步表征Malat1表达在骨骼肌肌发生中的作用。基于RT-PCR的C2C12和原代人骨骼肌细胞的定量揭示了成肌细胞分化为肌管期间Malat1 mRNA的显着且持续的上调（4至7倍; P <0.05）。相反，使用siRNA靶向敲除Malat1可通过阻止G0 / G1期的细胞生长来抑制成肌细胞增殖。这些结果表明Malat1是肌生长抑制素的新型下游靶标，具有相当大的调节肌发生的能力。通过抑制和/或逆转肌肉萎缩和浪费疾病，鉴定肌肉生长抑制素的新靶标将对再生生物学产生重要影响。

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