1900 S. Limestone, CTW 105, University of Kentucky, Lexington, KY 40536, USA.
FASEB J. 2014 Apr;28(4):1654-65. doi: 10.1096/fj.13-239426. Epub 2013 Dec 27.
Our aim in the current study was to determine the necessity of satellite cells for long-term muscle growth and maintenance. We utilized a transgenic Pax7-DTA mouse model, allowing for the conditional depletion of > 90% of satellite cells with tamoxifen treatment. Synergist ablation surgery, where removal of synergist muscles places functional overload on the plantaris, was used to stimulate robust hypertrophy. Following 8 wk of overload, satellite cell-depleted muscle demonstrated an accumulation of extracellular matrix (ECM) and fibroblast expansion that resulted in reduced specific force of the plantaris. Although the early growth response was normal, an attenuation of hypertrophy measured by both muscle wet weight and fiber cross-sectional area occurred in satellite cell-depleted muscle. Isolated primary myogenic progenitor cells (MPCs) negatively regulated fibroblast ECM mRNA expression in vitro, suggesting a novel role for activated satellite cells/MPCs in muscle adaptation. These results provide evidence that satellite cells regulate the muscle environment during growth.
我们在本研究中的目的是确定卫星细胞对于长期肌肉生长和维持的必要性。我们利用了一种 Pax7-DTA 转基因小鼠模型，通过给予他莫昔芬处理可实现对 >90%的卫星细胞的条件性耗竭。通过去神经支配手术（去除协同肌会使比目鱼肌承受功能性过载）来刺激强烈的肥大。在 8 周的超负荷后，卫星细胞耗竭的肌肉表现出细胞外基质（ECM）的积累和成纤维细胞的扩张，导致比目鱼肌的比特定力降低。尽管早期的生长反应是正常的，但卫星细胞耗竭的肌肉中，通过肌肉湿重和纤维横截面积测量的肥大程度都出现了衰减。分离的原代肌源性祖细胞（MPCs）在体外对成纤维细胞 ECM mRNA 表达进行负调控，这表明激活的卫星细胞/MPCs 在肌肉适应中具有新的作用。这些结果提供了证据表明卫星细胞在生长过程中调节肌肉环境。
