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Exercise enhances skeletal muscle regeneration by promoting senescence in fibro-adipogenic progenitors.
Nature Communications ( IF 14.7 ) Pub Date : 2020-02-14 , DOI: 10.1038/s41467-020-14734-x
Yuki Saito 1 , Takako S Chikenji 1, 2 , Takashi Matsumura 3 , Masako Nakano 1 , Mineko Fujimiya 1
Affiliation  

Idiopathic inflammatory myopathies cause progressive muscle weakness and degeneration. Since high-dose glucocorticoids might not lead to full recovery of muscle function, physical exercise is also an important intervention, but some exercises exacerbate chronic inflammation and muscle fibrosis. It is unknown how physical exercise can have both beneficial and detrimental effects in chronic myopathy. Here we show that senescence of fibro-adipogenic progenitors (FAPs) in response to exercise-induced muscle damage is needed to establish a state of regenerative inflammation that induces muscle regeneration. In chronic inflammatory myopathy model mice, exercise does not promote FAP senescence or resistance against tumor necrosis factor-mediated apoptosis. Pro-senescent intervention combining exercise and pharmacological AMPK activation reverses FAP apoptosis resistance and improves muscle function and regeneration. Our results demonstrate that the absence of FAP senescence after exercise leads to muscle degeneration with FAP accumulation. FAP-targeted pro-senescent interventions with exercise and pharmacological AMPK activation may constitute a therapeutic strategy for chronic inflammatory myopathy.

中文翻译:

运动可通过促进纤维成脂祖细胞衰老来增强骨骼肌再生。

特发性炎症性肌病会导致进行性肌无力和变性。由于大剂量糖皮质激素可能无法使肌肉功能完全恢复,因此体育锻炼也是一项重要的干预措施,但某些锻炼会加剧慢性炎症和肌肉纤维化。尚不清楚体育锻炼如何在慢性肌病中产生有益和有害的作用。在这里,我们表明,建立运动诱导的肌肉损伤所需的纤维化脂肪祖细胞(FAP)的衰老需要建立诱导肌肉再生的再生炎症状态。在慢性炎性肌病模型小鼠中,运动不会促进FAP衰老或抵抗肿瘤坏死因子介导的细胞凋亡。衰老前干预结合运动和药理AMPK激活可逆转FAP凋亡抗性并改善肌肉功能和再生。我们的结果表明,运动后FAP衰老的缺乏会导致FAP堆积导致肌肉变性。以FAP为靶点的具有运动和药理AMPK激活作用的衰老前干预措施可能构成慢性炎症性肌病的治疗策略。
更新日期:2020-02-14
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