Integrin-β1/FAK signaling is involved in electrical stimulation to prevent disuse muscular atrophy induced by tail suspension in mice.
TL;DR
Electrical stimulation upregulates the expression of the mechanosensor integrin β1 and enhances the phosphorylation of its downstream effector, FAK, in skeletal muscle, providing preclinical evidence supporting the role of the integrin-β1/FAK signaling pathway in electrical stimulation-mediated muscle preservation.
Abstract
Background
Electrical stimulation is a widely used method for preventing and treating disuse muscle atrophy; however, the underlying mechanisms remain incompletely examined. Integrins, a class of transmembrane cell adhesion receptors, are considered primary mechanosensors involved in load-induced muscle growth. However, no previous studies have demonstrated whether integrin β1 and its downstream FAK signaling pathway are involved in the prevention of disuse muscle atrophy via electrical stimulation. Our study hypothesized that mechanical signals generated by electrical induced muscle contraction activate integrins, thereby contributing to muscle atrophy prevention.
Materials And Methods
A disuse muscle atrophy model was constructed by tail suspending C57BL/6 mice for 2 weeks. The average physiological cross-sectional area, muscle strength, muscle fiber type, integrin β1, p-FAK, and p-p70S6K protein expression in the gastrocnemius and soleus muscles were measured following electrical stimulation.
Results
Mice in the tail suspension with electrical stimulation (TS + E) group exhibited significantly greater physiological cross-sectional area and muscle strength compared with the tail suspension (TS) group (p < 0.05). Additionally, integrin β1 expression was lower in the TS group compared with the control group (p < 0.05). In contrast, in the TS + E group, expression levels of integrin β1, FAK, p-mTOR, and p-p70s6k were elevated compared with the TS group (p < 0.05). In GAS and SOL, the p-p70s6k/p70s6k ratio was significantly higher in the TS + E group compared with the TS group (p < 0.05). In GAS, the p-FAK/FAK ratio was higher in the TS + E group compared with the TS group (p < 0.01). However, no significant difference in p-FAK/FAK ratio was observed between the two groups in SOL.
Conclusion
Electrical stimulation upregulates the expression of the mechanosensor integrin β1 and enhances the phosphorylation of its downstream effector, FAK, in skeletal muscle. These effects may contribute to the attenuation of disuse muscle atrophy, providing preclinical evidence supporting the role of the integrin-β1/FAK signaling pathway in electrical stimulation-mediated muscle preservation.