Bone marrow mesenchymal stem cell-derived exosomes alleviate septic lung injury in mice through TLR4/NF-κB signaling pathway
10.3969/j.issn.1000-4718.2025.08.016
- VernacularTitle:骨髓间充质干细胞外泌体通过TLR4/NF-κB信号通路减轻小鼠脓毒症肺损伤
- Author:
Jianshuang LU
1
;
Beibei WANG
;
Ting ZOU
;
Yanke ZHU
;
Yuanyuan SUN
Author Information
1. 温州医科大学附属第一医院医院感染管理部,浙江 温州 325100;温州医科大学附属第一医院儿科,浙江 温州 325100
- Publication Type:Journal Article
- Keywords:
mesenchymal stem cells;
exosome;
septic lung injury;
inflammation;
TLR4/NF-κB signaling pathway
- From:
Chinese Journal of Pathophysiology
2025;41(8):1596-1604
- CountryChina
- Language:Chinese
-
Abstract:
AIM:This study aims to investigate the therapeutic impact of bone marrow mesenchymal stem cell(MSC)-derived exosomes(MSC-Exos)on septic lung injury by targeting Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)signaling pathway.METHODS:MSC-Exos were isolated from bone marrow MSCs using ultracentrifugation.The exosomes were characterized by transmission electron microscopy(TEM),nanoparticle tracking analysis(NTA),and Western blot.A septic lung injury model was established via cecal ligation and puncture(CLP).MSC-Exos were adminis-tered intraperitoneally 3 h after CLP.Blood and lung tissue samples were collected at 6,12,24,and 72 h after CLP.Con-centrations of interleukin-10(IL-10),IL-6,IL-1β,and tumor necrosis factor-α(TNF-α)were measured by ELISA.The lung tissue damage in mice was assessed by HE staining.Expression levels of TLR4 and NF-κB were detected by RT-qP-CR and Western blot.RESULTS:The results of TEM revealed typical round and oval exosome-like structures of MSC-Exos.Western blot showed positive expression of CD63,TSG101 and HSP-70.The results of NTA indicated that the parti-cle size of MSC-Exos was(107.5±16.6)nm.Septic lung injury began to manifest 12 h after CLP and progressively worsened,peaking at 72 h after CLP.At 6 h after CLP,the level of TNF-α was markedly elevated compared to the control group,reaching its peak at 72 h after CLP.At 12 h after CLP,the levels of IL-1β,IL-10,and IL-6 were elevated com-pared to the control group,and they reached their maximum point 72 h post-CLP.The MSC-Exos intervention group ex-hibited significantly reduced lung injury compared to the CLP group,as indicated by the lung pathology scoring.In the MSC-Exos intervention group,concentrations of IL-10,IL-1β,IL-6,and TNF-α peaked at 12 h after CLP,gradually de-clined,and returned to baseline levels by 72 h.TLR4 and NF-κB expression levels were significantly increased at 6 h af-ter CLP in the CLP group,peaking at 72 h.In contrast,MSC-Exos treatment normalized TLR4 and NF-κB expression levels at 72 h after CLP.CONCLUSION:Early intervention with bone marrow MSC-Exos significantly alleviated septic lung injury by reducing the inflammatory cytokine storm,likely through downregulation of the TLR4/NF-κB signaling path-way.
