M2 macrophage-derived exosomes promote neural regeneration by enhancing proliferation of Schwann cells via the AKT-WEE1 pathway
10.3969/j.issn.1671-7856.2025.05.004
- VernacularTitle:M2型巨噬细胞外泌体通过AKT-WEE1通路促进SCs增殖增强神经再生
- Author:
Limao WU
1
;
Jinglan HE
;
Na SHEN
;
Song CHEN
Author Information
1. 河北工程大学临床医学院,河北邯郸 056004
- Publication Type:Journal Article
- Keywords:
macrophage;
exosome;
Schwann cells;
peripheral nerve injury;
WEE1
- From:
Chinese Journal of Comparative Medicine
2025;35(5):37-50
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism of action of macrophage-derived exosomes(Exo)in peripheral nerve injury(PNI).Methods Exo were extracted following the polarization of macrophages to either the M1 or M2 phenotype to determine their effects on Schwann cells(SCs),using cell proliferation,quantitative real-time polymerase chain reaction,flow cytometry,RNA sequencing,and Western blot.A sciatic nerve extrusion model was established in vivo.PBS,M1-exo and M2-exo treatment groups were injected with PBS,M1-exo,and M2-exo,respectively,and a separate normal group was set up.The sciatic nerve function index(SFI),wet weight ratio,and staining of neuromuscular tissue were evaluated on a weekly basis in each experimental group following surgical intervention.Results M1-exo facilitated SC migration and upregulated glial-derived nerve growth factor,whereas M2-exo promoted SC proliferation and migration and upregulated brain-derived nerve growth factor and nerve growth factor.The biomarkers,myelin protein zero,glial fibrillary acidic protein,nerve growth factor receptor(NGFR)and S100 calcium-binding protein B(S100)were also detected.In the in vivo experiments,the SFI,wet weight ratio,neuromuscular tissues,and fluorescent areas of nerve axons(marker NF200)and SCs(marker S100)were all significantly better in the M2-exo treatment group at week 4 compared with the PBS treatment group,while there were no significant differences between the M1-exo and PBS treatment groups.Both the in vivo and ex vivo experiments demonstrated that M2-exo facilitated the proliferation of SCs via phosphorylation of the serine/threonine kinase AKT,resulting in downregulation of the cell cycle protein WEE 1.Conclusions M2-exo has been demonstrated to promote up-regulation of genes associated with nerve regeneration by SCs and promote SC proliferation and migration,thereby facilitating nerve regeneration via the AKT-WEE1 pathway.
