Proteomics and Transcriptomics Analysis Reveals Clues into the Mechanism of the Beneficial Effect of Electrical Stimulation on Rat Denervated Gastrocnemius Muscle.

BACKGROUND/AIMS: The aim of this study was to confirm the beneficial effects of electrical stimulation on denervated skeletal muscle and explore a novel underlying mechanism.

METHODS

Morphological and contractile analyses were performed on rats allocated to three groups: sham operation (SHAM), denervated (DN), and denervated and electrical stimulation (DN-SM). Proteomics, transcriptomics, bioinformatics, and skeletal muscle functional modules analysis were conducted to determine the changes in molecular expression resulting from electrical stimulation.

RESULTS

Rats in the DN-SM group maintained a greater muscle mass, muscle fiber diameter, and contractile properties than those of the DN group. A total of 66 proteins and 402 mRNAs were differentially expressed between groups. Bioinformatics analysis suggested that the FoxO and p53 signaling pathways play significant roles in structural protection. Skeletal muscle function modules analysis suggested that anti-apoptosis proteins (KCNA7, KCNJ11), muscle fiber type related proteins (TNNI1, TNNT1, ACTN2, MYOZ2, MYLK2, and MYOM2), M-line structural protein (MYOM2), dystrophin combined with glycoprotein complex proteins (SGCB, SGCD, and DTNA), and anti-fibrosis-related proteins (POSTN, COL1A1, COL1A2, COL6A1, COL6A2, COL6A3, FN1, and LUM), may be related to the effects of electrical stimulation.

CONCLUSION

Electrical stimulation can maintain the denervated muscle morphology and function. Anti-apoptosis, inhibition of muscle fiber type differentiation, protection against dystrophin-associated-glycoprotein complex mutation, and anti-fibrosis are potential mechanisms of the beneficial effects of electrical stimulation.