E2 signaling in myofibers promots macrophage efferocytosis in mouse skeletal muscles with cardiotoxin-induced acute injury
10.12122/j.issn.1673-4254.2024.11.16
- VernacularTitle:肌纤维E2信号促进小鼠急性损伤骨骼肌内的巨噬细胞胞葬
- Author:
Qihui CAI
1
;
Haiqiang LAN
;
Bojun XIAN
;
Lian LIU
;
Nan WANG
;
Xiaolei HUANG
;
Xiaolu NIU
;
Xinyu HU
;
Chen LI
;
Junyi XIE
;
Zhaohong LIAO
Author Information
1. 佛山大学医学部 1医学技术教研室,广东 佛山 528000
- Keywords:
E2 signaling;
acute skeletal muscle injury;
macrophages efferocytosis;
inflammation
- From:
Journal of Southern Medical University
2024;44(11):2192-2200
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of E2 signaling in myofibers on muscular macrophage efferocytosis in mice with cardiotoxin-induced acute skeletal muscle injury.Methods Female wild-type C57BL/6 mice with and without ovariectomy and male C57BL/6 mice were given a CTX injection into the anterior tibial muscle to induce acute muscle injury,followed by intramuscular injection of β-estradiol(E2)or 4-hydroxytamoxifen(4-OHT).The changes in serum E2 of the mice were detected using ELISA,and the number,phenotypes,and efferocytosis of the macrophages in the inflammatory exudates and myofiber regeneration and repair were evaluated using immunofluorescence staining and flow cytometry.C2C12 cells were induced to differentiate into mature myotubes,which were treated with IFN-γ for 24 before treatment with β-Estradiol or 4-OHT.The treated myotubes were co-cultured with mouse peritoneal macrophages in a 1:2 ratio,followed by addition of PKH67-labeled apoptotic mouse mononuclear spleen cells induced by UV irradiation,and macrophage efferocytosis was observed using immunofluorescence staining and flow cytometry.Results Compared with the control mice,the female mice with ovariectomy showed significantly increased mononuclear macrophages in the inflammatory exudates,with increased M1 cell percentage,reduced M2 cell percentage and macrophage efferocytosis in the injured muscle,and obviously delayed myofiber regeneration and repair.In the cell co-culture systems,treatment of the myotubes with β-estradiol significantly increased the number and proportion of M2 macrophages and macrophage efferocytosis,while 4-OHT treatment resulted in the opposite changes.Conclusion In injured mouse skeletal muscles,myofiber E2 signaling promotes M1 to M2 transition to increase macrophage efferocytosis,thereby relieving inflammation and promoting muscle regeneration and repair.
