Abstract
Abstract
Strategies to delay the process of denervated muscle atrophy are limited, in part because the microenvironmental function of the target muscle is not well understood. Immune microenvironment remodelling is one of the main changes of skeletal muscle environment after denervation. Our previous work found that denervated atrophic muscles recruit a large number of neutrophils and macrophages, and neutrophils can delay muscle atrophy, but the specific mechanism is still unclear. In this study, the expression of
S100a8/S100a9
was significantly up-regulated in the transcriptional group of early denervated skeletal muscle. Immunofluorescence, flow sorting and quantitative PCR analysis showed that S100A8/S100A9 mainly came from neutrophils. Further knockout of
S100a9
has the same effect as blocking neutrophils to aggravate muscle atrophy. Through MerTK blockers, it is clear that MerTK
hi
Ly6C
lo
reparatory macrophages can delay the progression of muscle atrophy. After knockout of the
S100a9
gene, the mobilization of bone marrow haematopoietic stem cells decreased, the excretion of spleen monocytes was blocked, the number of peripheral blood monocytes decreased, the infiltration of monocytes/macrophages in target muscle decreased and the polarization of MerTK
hi
Ly6C
lo
reparatory macrophages was blocked. It is clear that S100A9 regulates the polarization of MerTK
hi
Ly6C
lo
reparative macrophages. Collectively, based on the interaction between neutrophils and macrophages, it is clear that S100A8/S100A9 participates in delaying the process of denervated muscle atrophy by promoting the polarization of MerTK
hi
Ly6C
lo
reparatory macrophages, and provides a new immune target for the early delay and prevention of denervated muscle atrophy.