Open AccessLysyl oxidase‐like 2 inhibitor rescues D‐galactose‐induced skeletal muscle fibrosis
Author(s) -
Wu Yongxin,
Wu Yaoxuan,
Yang Yunfei,
Yu Jing,
Wu Jianghao,
Liao Zhiyin,
Guo Ai,
Sun Yue,
Zhao Yuxing,
Chen Jinliang,
Xiao Qian
Publication year - 2022
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.13659
Subject(s) - lysyl oxidase , biology , skeletal muscle , fibrosis , galactose , galactose oxidase , biochemistry , medicine , microbiology and biotechnology , endocrinology , enzyme
Aging‐related sarcopenia is currently the most common sarcopenia. The main manifestations are skeletal muscle atrophy, replacement of muscle fibers with fat and fibrous tissue. Excessive fibrosis can impair muscle regeneration and function. Lysyl oxidase‐like 2 (LOXL2) has previously been reported to be involved in the development of various tissue fibrosis. Here, we investigated the effects of LOXL2 inhibitor on D‐galactose (D‐gal)‐induced skeletal muscle fibroblast cells and mice. Our molecular and physiological studies show that treatment with LOXL2 inhibitor can alleviate senescence, fibrosis, and increased production of reactive oxygen species in fibroblasts caused by D‐gal. These effects are related to the inhibition of the TGF‐β1/p38 MAPK pathway. Furthermore, in vivo, mice treatment with LOXL2 inhibitor reduced D‐gal‐induced skeletal muscle fibrosis, partially enhanced skeletal muscle mass and strength and reduced redox balance disorder. Taken together, these data indicate the possibility of using LOXL2 inhibitors to prevent aging‐related sarcopenia, especially with significant fibrosis.