Background: Skeletal muscle mass is defined by the homeostatic coordination of muscle degeneration and regeneration under various pathophysiological conditions. We have previously reported that iron accumulation induces skeletal muscle atrophy via the ubiquitin-ligase dependent pathway. However, the actionof iron on muscle myogenesis has remained unclear. In the present study, we investigated the effect of iron on skeletal muscle myogenesis.
Methods: We examined muscle regeneration by using cardiotoxin (CTX)-induced muscle injury mice model with or without iron overload in in vivo experiments, and C2C12 mice myoblast cells for in vitro study.
Results: In mice with iron overload, the skeletal muscles exhibited an increase in oxidative stress and a decrease in the expression of satellite cells markers such as Pax-7 and MyoD expression. Following CTX-induced muscle injury, mice with iron overload also exhibited delay in muscle regeneration with the reduced size of regenerating myofibres, decreased expression of myogenin and myosin heavy chain, and less phosphorylation of the p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) 1/2. Similarly to the findings in the in vivo experiments, iron treatment also inhibited C2C12 myoblast cells differentiation, and it was ameliorated by a superoxide scavenger drug.
Conclusion: Iron accumulation suppresses skeletal muscle myogenesis through inhibiting MAPKs signalling via oxidative stress, causing an imbalance in the skeletal muscle homeostasis.
