Myostatin suppression of Akirin1 mediates glucocorticoid-induced satellite cell dysfunction.
Myostatin suppression of Akirin1 mediates glucocorticoid-induced satellite cell dysfunction.
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DOI：
10.1371/journal.pone.0058554
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Dong Y;Pan JS;Zhang L
糖皮质激素的产生在许多与肌肉损失相关的病理条件下增加，但它们在导致肌肉萎缩中的作用尚未完全了解。我们已经证明了糖皮质激素诱导的肌肉萎缩的新机制：地塞米松（Dex）抑制卫星细胞功能，有助于肌肉萎缩的发展。具体来说，我们发现Dex在体外和体内降低卫星细胞增殖和分化。其机制涉及右旋糖酐诱导的肌肉生长抑制素上调和抑制Akirin1，一个promyogenic基因。当肌肉生长抑制素在右旋糖酐处理的小鼠中被抑制时，Akirin1表达增加，卫星细胞活性、肌肉再生和肌肉生长也增加。此外，沉默成肌细胞或卫星细胞中的肌生长抑制素阻止了Dex抑制Akirin1表达以及细胞增殖和分化。最后，Akirin1在成肌细胞中的过表达增加了它们的MyoD和肌细胞生成素的表达，并改善了细胞增殖和分化，这些改善不再被Dex抑制。我们的结论是，糖皮质激素刺激肌肉生长抑制素抑制Akirin1的表达和卫星细胞的修复功能。这些反应归因于肌肉萎缩。因此，抑制肌肉生长抑制素或增加Akirin1表达可能导致改善卫星细胞活化和增强与糖皮质激素产生增加相关的疾病的肌肉生长的治疗策略。
Glucocorticoids production is increased in many pathological conditions that are associated with muscle loss, but their role in causing muscle wasting is not fully understood. We have demonstrated a new mechanism of glucocorticoid-induced muscle atrophy: Dexamethasone (Dex) suppresses satellite cell function contributing to the development of muscle atrophy. Specifically, we found that Dex decreases satellite cell proliferation and differentiation in vitro and in vivo. The mechanism involved Dex-induced upregulation of myostatin and suppression of Akirin1, a promyogenic gene. When myostatin was inhibited in Dex-treated mice, Akirin1 expression increased as did satellite cell activity, muscle regeneration and muscle growth. In addition, silencing myostatin in myoblasts or satellite cells prevented Dex from suppressing Akirin1 expression and cellular proliferation and differentiation. Finally, overexpression of Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation, theses improvements were no longer suppressed by Dex. We conclude that glucocorticoids stimulate myostatin which inhibits Akirin1 expression and the reparative functions of satellite cells. These responses attribute to muscle atrophy. Thus, inhibition of myostatin or increasing Akirin1 expression could lead to therapeutic strategies for improving satellite cell activation and enhancing muscle growth in diseases associated with increased glucocorticoid production.
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影响因子：
3.7
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