Goh Qingnian, Millay Douglas P
Department of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States.
Elife. 2017 Feb 10;6:e20007. doi: 10.7554/eLife.20007.
Fusion of skeletal muscle stem/progenitor cells is required for proper development and regeneration, however the significance of this process during adult muscle hypertrophy has not been explored. In response to muscle overload after synergist ablation in mice, we show that myomaker, a muscle specific membrane protein essential for myoblast fusion, is activated mainly in muscle progenitors and not myofibers. We rendered muscle progenitors fusion-incompetent through genetic deletion of myomaker in muscle stem cells and observed a complete reduction of overload-induced hypertrophy. This blunted hypertrophic response was associated with a reduction in Akt and p70s6k signaling and protein synthesis, suggesting a link between myonuclear accretion and activation of pro-hypertrophic pathways. Furthermore, fusion-incompetent muscle exhibited increased fibrosis after muscle overload, indicating a protective role for normal stem cell activity in reducing myofiber strain associated with hypertrophy. These findings reveal an essential contribution of myomaker-mediated stem cell fusion during physiological adult muscle hypertrophy.
骨骼肌干/祖细胞的融合对于正常发育和再生是必需的，然而这一过程在成年肌肉肥大过程中的意义尚未得到探索。在小鼠协同肌切除后肌肉过载的情况下，我们发现肌生成素（一种对成肌细胞融合至关重要的肌肉特异性膜蛋白）主要在肌肉祖细胞而非肌纤维中被激活。我们通过基因敲除肌肉干细胞中的肌生成素使肌肉祖细胞失去融合能力，并观察到过载诱导的肥大完全减少。这种减弱的肥大反应与Akt和p70s6k信号传导及蛋白质合成的减少有关，提示肌核增加与促肥大途径的激活之间存在联系。此外，融合能力缺失的肌肉在肌肉过载后表现出纤维化增加，表明正常干细胞活性在减少与肥大相关的肌纤维应变方面具有保护作用。这些发现揭示了肌生成素介导的干细胞融合在生理性成年肌肉肥大过程中的重要贡献。
