中国比较医学杂志2025，Vol.35Issue(5)：37-50,14.DOI:10.3969/j.issn.1671-7856.2025.05.004
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
M2 macrophage-derived exosomes promote neural regeneration by enhancing proliferation of Schwann cells via the AKT-WEE1 pathway
摘要
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.关键词
巨噬细胞/外泌体/雪旺细胞/周围神经损伤/WEE1Key words
macrophage/exosome/Schwann cells/peripheral nerve injury/WEE1引用本文复制引用
吴礼毛,贺靖澜,申娜,陈松..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[J].中国比较医学杂志,2025,35(5):37-50,14.基金项目
河北省卫生健康委员会2023医学科学研究项目(20231515) （20231515）
河北省优秀人才培养项目(ZF2024207). （ZF2024207）
