Pyruvate dehydrogenase B regulates myogenic differentiation via the FoxP1–Arih2 axis

作者：Xuan Jiang, Siyu Ji, Feng‐Lai Yuan, Tushuai Li, Siyuan Cui, Wei Wang, Xianlong Ye, Rong Wang, Yong Q. Chen, Shenglong Zhu · 发表于：Journal of Cachexia Sarcopenia and Muscle · 年份：2022 · DOI：10.1002/jcsm.13166 · 被引用次数：45 · 研究领域：Biochemical Acid Research Studies、Cancer, Hypoxia, and Metabolism、Metabolism and Genetic Disorders

BACKGROUND: Sarcopenia, the age-related decline in skeletal muscle mass and function, diminishes life quality in elderly people. Improving the capacity of skeletal muscle differentiation is expected to counteract sarcopenia. However, the mechanisms underlying skeletal muscle differentiation are complex, and effective therapeutic targets are largely unknown. METHODS: The human Gene Expression Omnibus database, aged mice and primary skeletal muscle cells were used to assess the expression level of pyruvate dehydrogenase B (PDHB) in human and mouse aged state. d-Galactose (d-gal)-induced sarcopenia mouse model and two classic cell models (C2C12 and HSkMC) were used to assess the myogenic effect of PDHB and the underlying mechanisms via immunocytochemistry, western blotting, quantitative real-time polymerase chain reaction, RNA interference or overexpression, dual-luciferase reporter assay, RNA sequencing and untargeted metabolomics. RESULTS: We identified that a novel target PDHB promoted myogenic differentiation. PDHB expression decreased in aged mouse muscle relative to the young state (-50% of mRNA level, P < 0.01) and increased during mouse and primary human muscle cell differentiation (+3.97-fold, P < 0.001 and +3.79-fold, P < 0.001). Knockdown or overexpression of PDHB modulated the expression of genes related to muscle differentiation, namely, myogenic factor 5 (Myf5) (-46%, P < 0.01 and -27%, P < 0.05; +1.8-fold, P < 0.01), myogenic differentiation (MyoD) (-55%, P < 0.00...