Stigmasterol alleviates neuropathic pain by reducing Schwann cell-macrophage cascade in DRG by modulating IL-34/CSF1R.
CCI
CSF1R
DRG
IL‐34
single‐cell sequencing
stigmasterol
Journal
CNS neuroscience & therapeutics
ISSN: 1755-5949
Titre abrégé: CNS Neurosci Ther
Pays: England
ID NLM: 101473265
Informations de publication
Date de publication:
Apr 2024
Apr 2024
Historique:
revised:
04
01
2024
received:
23
05
2023
accepted:
25
01
2024
medline:
4
4
2024
pubmed:
4
4
2024
entrez:
4
4
2024
Statut:
ppublish
Résumé
This study aimed to investigate the potential therapeutic applications of stigmasterol for treating neuropathic pain. Related mechanisms were investigated by DRG single-cell sequencing analysis and the use of specific inhibitors in cellular experiments. In animal experiments, 32 male Sprague-Dawley rats were randomly divided into the sham operation group, CCI group, ibuprofen group, and stigmasterol group. We performed behavioral tests, ELISA, H&E staining and immunohistochemistry, and western blotting. Cell communication analysis by single-cell sequencing reveals that after peripheral nerve injury, Schwann cells secrete IL-34 to act on CSF1R in macrophages. After peripheral nerve injury, the mRNA expression levels of CSF1R pathway and NLRP3 inflammasome in macrophages were increased in DRG. In vitro studies demonstrated that stigmasterol can reduce the secretion of IL-34 in LPS-induced RSC96 Schwann cells; stigmasterol treatment of LPS-induced Schwann cell-conditioned medium (L-S-CM) does not induce the proliferation and migration of RAW264.7 macrophages; L-S-CM reduces CSF1R signaling pathway (CSF1R, P38MAPK, and NFκB) activation, NLRP3 inflammasome activation, and ROS production. In vivo experiments have verified that stigmasterol can reduce thermal and cold hyperalgesia in rat chronic compressive nerve injury (CCI) model; stigmasterol can reduce IL-1β, IL-6, TNF-α, CCL2, SP, and PGE2 in serum of CCI rats; immunohistochemistry and western blot confirmed that stigmasterol can reduce the levels of IL-34/CSF1R signaling pathway and NLRP3 inflammasome in DRG of CCI rats. Stigmasterol alleviates neuropathic pain by reducing Schwann cell-macrophage cascade in DRG by modulating IL-34/CSF1R axis.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14657Subventions
Organisme : China Postdoctoral Science Foundation
ID : 2023TQ0135
Organisme : Postdoctoral Fellowship Program of CPSF
ID : GZC20230979
Organisme : National Natural Science Foundation of China
ID : 82105047
Organisme : National Natural Science Foundation of China
ID : 82274294
Informations de copyright
© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.
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