Muscle regeneration in the prolonged absence of myostatin
Muscle regeneration in the prolonged absence of myostatin
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DOI：
10.1073/pnas.0408729102
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发表时间：
2005-02-15
影响因子：
11.1
通讯作者：
Allen, RE
中科院分区：
文献类型：
--
作者：
Wagner, KR;Liu, XS;Allen, RE
肌肉生长抑制素是一种在不同物种中保守的肌肉内源性抑制剂。在缺乏肌肉生长抑制素的情况下，小鼠、牛和人类的肌肉会大量生长。先前对肌营养不良症 mdx 小鼠模型的研究表明，抑制肌生长抑制素可以减弱营养不良性肌肉的几个特征。这些发现鼓励了人类疗法的开发来阻断肌肉生长抑制素。然而，人们对肌生长抑制素阻断对肌肉的长期影响知之甚少。为了评估长期缺乏肌生长抑制素引起的潜在后遗症，研究了衰老的肌生长抑制素无效（mstn（-/-））小鼠。衰老的 mstn(-/-) 小鼠继续具有正常肌肉，但相对于对照组，其质量和强度有所增加。衰老的 mstn(-/-) 小鼠的肌肉在慢性和急性损伤中都能强劲再生。在缺乏肌生长抑制素的情况下，再生的早期标志物会增强，这表明缺乏肌生长抑制素的 mdx 小鼠中发现的营养不良特征减弱的机制。
Myostatin is an endogenous inhibitor of muscle conserved across diverse species. In the absence of myostatin, there is massive muscle growth in mice, cattle, and humans. Previous studies in the mdx mouse model of muscular dystrophy demonstrate that inhibiting myostatin attenuates several features of dystrophic muscle. These findings have encouraged the development of human therapies to block myostatin. However, little is known of the long-term effects on muscle of myostatin blockade. To evaluate potential sequelae from the prolonged absence of myostatin, senescent myostatin null (mstn(-/-)) mice were studied. Senescent mstn(-/-) mice continue to have normal muscle with increased mass and strength relative to controls. Muscles of senescent mstn(-/-) mice regenerate robustly from both chronic and acute injury. Early markers of regeneration are enhanced in the absence of myostatin, suggesting a mechanism for the attenuation of dystrophic features found in mdx mice lacking myostatin.