Teo Wan-Huai, Lo Jeng-Fan, Fan Yu-Ning, Huang Chih-Yang, Huang Tung-Fu
Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan.
Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan.
PLoS One. 2020 Dec 31;15(12):e0244791. doi: 10.1371/journal.pone.0244791. eCollection 2020.
Ageing and chronic diseases lead to muscle loss and impair the regeneration of skeletal muscle. Thus, it's crucial to seek for effective intervention to improve the muscle regeneration. Tid1, a mitochondrial co-chaperone, is important to maintain mitochondrial membrane potential and ATP synthesis. Previously, we demonstrated that mice with skeletal muscular specific Tid1 deficiency displayed muscular dystrophy and postnatal lethality. Tid1 can interact with STAT3 protein, which also plays an important role during myogenesis. In this study, we used GMI, immunomodulatory protein of Ganoderma microsporum, as an inducer in C2C12 myoblast differentiation. We observed that GMI pretreatment promoted the myogenic differentiation of C2C12 myoblasts. We also showed that the upregulation of mitochondria protein Tid1 with the GMI pre-treatment promoted myogenic differentiation ability of C2C12 cells. Strikingly, we observed the concomitant elevation of STAT3 acetylation (Ac-STAT3) during C2C12 myogenesis. Our study suggests that GMI promotes the myogenic differentiation through the activation of Tid1 and Ac-STAT3.
衰老和慢性疾病会导致肌肉流失,并损害骨骼肌的再生。因此,寻找有效的干预措施来改善肌肉再生至关重要。Tid1是一种线粒体共伴侣蛋白,对维持线粒体膜电位和ATP合成很重要。此前,我们证明骨骼肌特异性Tid1缺陷的小鼠表现出肌肉萎缩和出生后致死性。Tid1可与STAT3蛋白相互作用,而STAT3在肌生成过程中也起着重要作用。在本研究中,我们使用灵芝微孢子免疫调节蛋白GMI作为C2C12成肌细胞分化的诱导剂。我们观察到GMI预处理促进了C2C12成肌细胞的肌源性分化。我们还表明,GMI预处理使线粒体蛋白Tid1上调,促进了C2C12细胞的肌源性分化能力。引人注目的是,我们在C2C12肌生成过程中观察到STAT3乙酰化(Ac-STAT3)同时升高。我们的研究表明,GMI通过激活Tid1和Ac-STAT3促进肌源性分化。