Project for Muscle Stem Cell Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
Faculty of Sport Sciences, Waseda University, Saitama, Japan.
Biochim Biophys Acta Mol Cell Res. 2020 Sep;1867(9):118742. doi: 10.1016/j.bbamcr.2020.118742. Epub 2020 May 14.
Skeletal muscle is a dynamic tissue with two unique abilities; one is its excellent regenerative ability, due to the activity of skeletal muscle-resident stem cells named muscle satellite cells (MuSCs); and the other is the adaptation of myofiber size in response to external stimulation, intrinsic factors, or physical activity, which is known as plasticity. Low physical activity and some disease conditions lead to the reduction of myofiber size, called atrophy, whereas hypertrophy refers to the increase in myofiber size induced by high physical activity or anabolic hormones/drugs. MuSCs are essential for generating new myofibers during regeneration and the increase in new myonuclei during hypertrophy; however, there has been little investigation of the molecular mechanisms underlying MuSC activation, proliferation, and differentiation during hypertrophy compared to those of regeneration. One reason is that 'degenerative damage' to myofibers during muscle injury or upon hypertrophy (especially overloaded muscle) is believed to trigger similar activation/proliferation of MuSCs. However, evidence suggests that degenerative damage of myofibers is not necessary for MuSC activation/proliferation during hypertrophy. When considering MuSC-based therapy for atrophy, including sarcopenia, it will be indispensable to elucidate MuSC behaviors in muscles that exhibit non-degenerative damage, because degenerated myofibers are not present in the atrophied muscles. In this review, we summarize recent findings concerning the relationship between MuSCs and hypertrophy, and discuss what remains to be discovered to inform the development and application of relevant treatments for muscle atrophy.
骨骼肌是一种具有两种独特能力的动态组织；一种是其出色的再生能力，这归因于骨骼肌驻留的干细胞，即肌肉卫星细胞（MuSCs）的活性；另一种是肌纤维大小对外界刺激、内在因素或体育活动的适应，这被称为可塑性。低体育活动和一些疾病状况会导致肌纤维大小减少，称为萎缩，而肥大则是指高体育活动或合成代谢激素/药物引起的肌纤维大小增加。MuSCs 对于在再生过程中产生新的肌纤维以及在肥大过程中增加新的肌核是必不可少的；然而，与再生相比，MuSC 在肥大过程中的激活、增殖和分化的分子机制的研究还很少。一个原因是，人们认为肌纤维在肌肉损伤或肥大时（尤其是超负荷肌肉）的“退行性损伤”会引发 MuSCs 的类似激活/增殖。然而，有证据表明，肥大过程中肌纤维的退行性损伤对于 MuSC 的激活/增殖并不是必需的。在考虑基于 MuSC 的治疗萎缩症（包括肌肉减少症）时，阐明在没有退行性损伤的肌肉中 MuSC 的行为将是必不可少的，因为萎缩的肌肉中不存在退化的肌纤维。在这篇综述中，我们总结了最近关于 MuSCs 与肥大之间关系的研究结果，并讨论了为了为肌肉萎缩症的相关治疗的开发和应用提供信息，还有哪些需要发现的问题。
