Mitochondrial glycerol 3-phosphate dehydrogenase promotes skeletal muscle regeneration.
Mitochondrial glycerol 3-phosphate dehydrogenase promotes skeletal muscle regeneration.
复制标题
线粒体甘油3-磷酸脱氢酶促进骨骼肌再生
DOI：
10.15252/emmm.201809390
复制
发表时间：
2018-12
影响因子：
11.1
通讯作者：
Zheng H
中科院分区：
文献类型：
--
作者：
Liu X;Qu H;Zheng Y;Liao Q;Zhang L;Liao X;Xiong X;Wang Y;Zhang R;Wang H;Tong Q;Liu Z;Dong H;Yang G;Zhu Z;Xu J;Zheng H
虽然成年哺乳动物骨骼肌由于其有丝分裂后的性质而稳定，但肌肉再生对于维持功能适应性在整个生命中仍然是必不可少的。在某些疾病期间，例如肥胖和糖尿病的现代流行病，再生过程受到损害，这导致肌肉功能丧失，并导致这些疾病的全球负担。然而，受损的潜在机制尚未明确。在这里，我们确定mGPDH作为骨骼肌再生的关键调节因子。具体而言，它通过CaMKKβ/AMPK控制线粒体生物发生来调节肌源性标志物和成肌细胞分化。mGPDH−/−在体外和体内减弱了骨骼肌再生，而mGPDH过表达改善了mdx小鼠的营养不良病理。此外，在肥胖和糖尿病患者和动物模型中，骨骼肌中的mGPDH表达减少，进一步表明其丰度与肌肉再生能力之间存在直接相关性。在肥胖和糖尿病小鼠中拯救mGPDH表达导致其肌肉再生的显着改善。我们的研究为肥胖和糖尿病期间骨骼肌再生障碍提供了潜在的治疗靶点。
While adult mammalian skeletal muscle is stable due to its post‐mitotic nature, muscle regeneration is still essential throughout life for maintaining functional fitness. During certain diseases, such as the modern pandemics of obesity and diabetes, the regeneration process becomes impaired, which leads to the loss of muscle function and contributes to the global burden of these diseases. However, the underlying mechanisms of the impairment are not well defined. Here, we identify mGPDH as a critical regulator of skeletal muscle regeneration. Specifically, it regulates myogenic markers and myoblast differentiation by controlling mitochondrial biogenesis via CaMKKβ/AMPK. mGPDH−/− attenuated skeletal muscle regeneration in vitro and in vivo, while mGPDH overexpression ameliorated dystrophic pathology in mdx mice. Moreover, in patients and animal models of obesity and diabetes, mGPDH expression in skeletal muscle was reduced, further suggesting a direct correlation between its abundance and muscular regeneration capability. Rescuing mGPDH expression in obese and diabetic mice led to a significant improvement in their muscle regeneration. Our study provides a potential therapeutic target for skeletal muscle regeneration impairment during obesity and diabetes.