Department of Pharmacology and Physiology, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
Centre Hospitalier Universitaire (CHU) Sainte-Justine Research Center, Montreal, QC, Canada.
Biosci Rep. 2023 Jan 31;43(1). doi: 10.1042/BSR20220284.
Skeletal muscle possesses a high plasticity and a remarkable regenerative capacity that relies mainly on muscle stem cells (MuSCs). Molecular and cellular components of the MuSC niche, such as immune cells, play key roles to coordinate MuSC function and to orchestrate muscle regeneration. An abnormal infiltration of immune cells and/or imbalance of pro- and anti-inflammatory cytokines could lead to MuSC dysfunctions that could have long lasting effects on muscle function. Different genetic variants were shown to cause muscular dystrophies that intrinsically compromise MuSC function and/or disturb their microenvironment leading to impaired muscle regeneration that contributes to disease progression. Alternatively, many acquired myopathies caused by comorbidities (e.g., cardiopulmonary or kidney diseases), chronic inflammation/infection, or side effects of different drugs can also perturb MuSC function and their microenvironment. The goal of this review is to comprehensively summarize the current knowledge on acquired myopathies and their impact on MuSC function. We further describe potential therapeutic strategies to restore MuSC regenerative capacity.
骨骼肌具有很高的可塑性和显著的再生能力，主要依赖于肌肉干细胞（MuSCs）。MuSC 生态位的分子和细胞成分，如免疫细胞，在协调 MuSC 功能和协调肌肉再生方面起着关键作用。免疫细胞的异常浸润和/或促炎和抗炎细胞因子的失衡可导致 MuSC 功能障碍，从而对肌肉功能产生持久影响。不同的遗传变异被证明会导致肌肉疾病，这些疾病本质上会损害 MuSC 的功能，或扰乱其微环境，导致受损的肌肉再生，从而促进疾病的进展。此外，许多由合并症（如心肺或肾脏疾病）、慢性炎症/感染或不同药物的副作用引起的获得性肌病也会干扰 MuSC 的功能及其微环境。本综述的目的是全面总结获得性肌病及其对 MuSC 功能的影响的现有知识。我们进一步描述了恢复 MuSC 再生能力的潜在治疗策略。
