Irisin ameliorates D-galactose-induced skeletal muscle fibrosis via the PI3K/Akt pathway
Yaoxuan Wu, Yongxin Wu, Jing Yu, Yingxiao Zhang, Yuanfen Li, Rao Fu, Yue Sun, Kexiang Zhao, Qian Xiao
Abstract
Primary sarcopenia is a multicausal skeletal muscle disease associated with muscle strength and mass loss. Skeletal muscle fibrosis is one of the significant pathological manifestations associated with the development of age-related sarcopenia. Irisin, which is cleaved by the extracellular domain of fibronectin type Ⅲ domain-containing protein 5 (FNDC5), has previously been reported to exert antifibrotic effects on the heart, liver, and pancreas, but whether it can rescue skeletal muscle fibrosis remains unknown. In this study, we examined the effects of irisin on D-galactose (D-gal)-induced skeletal muscle fibroblasts. We found that D-gal-induced senescence, fibrosis, and redox imbalance were inhibited by irisin treatment. Mechanistically, irisin or FNDC5 overexpression attenuated D-gal-induced senescence, redox imbalance, and fibrosis by regulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Overall, irisin might be a promising therapeutic candidate for age-related skeletal muscle fibrosis.