Myogenin regulates denervation-dependent muscle atrophy in mouse soleus muscle.
Myogenin regulates denervation-dependent muscle atrophy in mouse soleus muscle.
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DOI：
10.1002/jcb.23136
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发表时间：
2011-08
影响因子：
4
通讯作者：
Goldman, Daniel
中科院分区：
文献类型：
--
作者：
Macpherson, Peter C. D.;Wang, Xun;Goldman, Daniel
由于受伤或疾病导致的肌肉不活动导致肌肉萎缩。人们对导致肌肉萎缩的分子机制知之甚少。然而，很明显，萎缩相关基因的表达，如Atrogin-1和MuRF-1，与肌肉质量的损失密切相关。当这些萎缩相关基因被敲除时，不活动的肌肉保持质量。肌肉去神经刺激肌肉萎缩，肌细胞生成素（Myog）是肌肉去神经后高度诱导的肌肉特异性转录因子。为了研究Myog是否有助于肌肉萎缩，我们利用了条件性Myog缺失小鼠。我们发现，在失神经比目鱼肌肌表达有助于减少肌肉力量，质量和横截面积。我们发现Myog至少部分通过调节Atrogin-1和MuRF-1基因的表达来介导这些效应。事实上，在神经支配的肌肉中Myog过表达刺激Atrogin-1基因表达，Myog过表达刺激Atrogin-1启动子活性。因此，肌球蛋白和信号级联调节其诱导肌肉去神经后，可能代表新的目标，旨在减少去神经诱导的肌肉萎缩的治疗。
Muscle inactivity due to injury or disease results in muscle atrophy. The molecular mechanisms contributing to muscle atrophy are poorly understood. However, it is clear that expression of atrophy-related genes, like Atrogin-1 and MuRF-1, are intimately tied to loss of muscle mass. When these atrophy-related genes are knocked out, inactive muscles retain mass. Muscle denervation stimulates muscle atrophy and Myogenin (Myog) is a muscle-specific transcription factor that is highly induced following muscle denervation. To investigate if Myog contributes to muscle atrophy, we have taken advantage of conditional Myog null mice. We show that in the denervated soleus muscle Myog expression contributes to reduced muscle force, mass and cross sectional area. We found that Myog mediates these effects, at least in part, by regulating expression of the Atrogin-1 and MuRF-1 genes. Indeed Myog over-expression in innervated muscle stimulates Atrogin-1 gene expression and Myog over-expression stimulates Atrogin-1 promoter activity. Thus Myog and the signaling cascades regulating its induction following muscle denervation may represent novel targets for therapies aimed at reducing denervation-induced muscle atrophy.
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影响因子：
4.8
作者：
Cohen, Todd J.;Waddell, David S.;Yao, Tso-Pang
通讯作者：
Yao, Tso-Pang
影响因子：
4.8
作者：
Sacheck, Jennifer M.;Hyatt, Jon-Philippe K.;Goldberg, Alfred L.
通讯作者：
Goldberg, Alfred L.
DOI：
10.1152/ajpregu.2000.279.1.r179
发表时间：
2000-07-01
影响因子：
2.8
作者：
Kostrominova, TY;Macpherson, PCD;Goldman, D
通讯作者：
Goldman, D
影响因子：
4.8
作者：
Tang, HB;Veldman, MB;Goldman, D
通讯作者：
Goldman, D
影响因子：
5.5
作者：
BROOKS, SV;FAULKNER, JA
通讯作者：
FAULKNER, JA