Ganoderma microsporum immunomodulatory protein, GMI, promotes C2C12 myoblast differentiation in vitro via upregulation of Tid1 and STAT3 acetylation

Abstract

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.

Safety assessment of the fungal immunomodulatory protein from Ganoderma microsporum (GMI) derived from engineered Pichia pastoris: Genetic toxicology, a 13-week oral gavage toxicity study, and an embryo-fetal developmental toxicity study in Sprague-Dawley rats

“…A 2.0 Å structure of GMI was solved and GMI showed a dimer:dimer quaternary structure with non-covalent interactions through the N-terminal helices (PDB ID 3KCW, [16] ). Furthermore, GMI with the same quality were evaluated in the platform for the anti-tumor activity and immunomodulation under immune disorder/disease model, and GMI showed a variety of bioactivities in the application for oncology [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [44] , [43] , immuno-oncology [53] , [54] , [55] , [56] , [57] , and immunology [59] , [60] , [62] , [63] , [64] , [61] , [58] , [65] . Although these promising findings are attractive for the further clinical application, the quality and the safety are always the major concerns.…”