Irisin alters D-galactose-induced apoptosis by increasing caveolin-1 expression in C2C12 myoblasts and skeletal muscle fibroblasts

Mol Cell Biochem. 2025 Jan;480(1):577-588. doi: 10.1007/s11010-024-04990-6. Epub 2024 Apr 6.

Abstract

Muscle atrophy and skeletal muscle fibrosis are significant pathological manifestations of primary sarcopenia. The regulation of C2C12 myoblast and skeletal muscle fibroblast apoptosis is associated with these pathological changes. Previous studies have indicated that irisin, the cleaved form of fibronectin type III domain-containing protein 5 (FNDC5), can alleviate primary sarcopenia. However, the mechanisms of the effect of irisin in age-related apoptosis remain unknown. Our present research aimed to explore the effect of irisin and the underlying mechanism of D-galactose (D-gal)-induced apoptosis in skeletal muscle fibroblasts and C2C12 myoblasts. We found the opposite effects of D-gal on C2C12 myoblasts and fibroblasts. We also found that irisin suppressed C2C12 cell apoptosis and promoted fibroblast apoptosis. Mechanistically, irisin altered D-gal-induced apoptosis by increasing caveolin-1 expression. Taken together, these findings further demonstrated that irisin is a potential agent that can treat aged-relative muscle atrophy and fibrosis.

Keywords: Apoptosis; C2C12; Fibroblast; Irisin; Sarcopenia.

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Caveolin 1* / metabolism
  • Cell Line
  • Fibroblasts* / drug effects
  • Fibroblasts* / metabolism
  • Fibroblasts* / pathology
  • Fibronectins* / metabolism
  • Fibronectins* / pharmacology
  • Galactose* / pharmacology
  • Gene Expression Regulation / drug effects
  • Mice
  • Muscle, Skeletal* / drug effects
  • Muscle, Skeletal* / metabolism
  • Muscle, Skeletal* / pathology
  • Myoblasts* / drug effects
  • Myoblasts* / metabolism

Substances

  • Caveolin 1
  • Galactose
  • Fibronectins
  • FNDC5 protein, mouse
  • Cav1 protein, mouse