A link between mitochondrial damage and the immune microenvironment of delayed onset muscle soreness

Abstract

Background: Delayed onset muscle soreness (DOMS) is a self-healing muscle pain disorder. Inflammatory pain is the main feature of DOMS. More and more researchers have realized that changes in mitochondrial morphology are related to pain. However, the role of mitochondria in the pathogenesis of DOMS and the abnormal immune microenvironment is still unknown. Methods: Mitochondria-related genes and gene expression data were obtained from MitoCarta3.0 and NCBI GEO databases. The network of mitochondrial function and the immune microenvironment of DOMS was constructed by computer algorithm. Subsequently, the skeletal muscle of DOMS rats was subjected to qPCR to verify the bioinformatics results. DOMS and non-DOMS histological samples were further studied by staining and transmission electron microscopy. Results: Bioinformatics results showed that expression of mitochondria-related genes was changed in DOMS. The results of qPCR showed that four hub genes (AMPK, PGC1-α, SLC25A25, and ARMCX1) were differentially expressed in DOMS. These hub genes are related to the degree of skeletal muscle immune cell infiltration, mitochondrial respiratory chain complex, DAMPs, the TCA cycle, and mitochondrial metabolism. Bayesian network inference showed that IL-6 and PGC1-α may be the main regulatory genes of mitochondrial damage in DOMS. Transmission electron microscopy revealed swelling of skeletal muscle mitochondria and disorganization of myofilaments. Conclusions: Our study found that skeletal muscle mitochondrial damage is one of the causes of inflammatory factor accumulation in DOMS. According to the screened-out hub genes, this study provides a reference for follow-up clinical application.