miR-145 regulates immune function through Notch pathway and mediates neuroprotection of inflammatory response after traumatic brain injury
10.3969/j.issn.1000-484X.2024.03.009
- VernacularTitle:miR-145通过Notch通路调节免疫功能及炎症反应介导创伤性脑损伤的神经保护
- Author:
Dexian HU
1
;
Yanchang SUN
;
Jigao FENG
;
Yehe MO
Author Information
1. 海南医学院第二附属医院神经外科,海口 570311
- Keywords:
miR-145;
Traumatic brain injury;
Inflammation;
Immune regulation;
Notch signaling pathway
- From:
Chinese Journal of Immunology
2024;40(3):497-502
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role of miR-145 in inflammatory response and immune regulation after traumatic brain injury(TBI).Methods:Male C57BL/6 mice were randomly divided into sham operation group(Sham),model group(TBI),TBI+NC agomir group and TBI+miR-145 agomir group.Modified Nerve Injury Severity Score(mNSS)was used to evaluate neurological function after trauma.MWM test was used toevaluates neurocognitive function of mice after TBI.Flow cytometry was used to detect the number of Tregs in tbrain tissue of each group of mice.ELISA was used to detect expressions of inflammatory cytokines in hippocampus of each group of mice.Immunohistochemistry was used to detect expression of activated microglia/macrophage Iba-1 in hippocampus of each group of mice.RT-qPCR was used to detect expressions of M1/M2 microglia/macrophage marker genes iNOS,CD11b,CD206 and Arg1.TUNEL staining and neuronal nuclear immunity double staining with fluorescent label(NeuN)were used to detect neuronal apoptosis.Results:Compared with Sham group,expression of miR-145 in hippocampus of mice in TBI group was significantly decreased,the neurological damage was increased,and percentage of Tregs in CD4+T cell population in brain tissue was decreased.Expression levels of IL-1β,IL-6,TNF-α,IL-4,IL-10 and TGF-β in hippocampus were significantly increased,the number of activated microglia/macrophage IBA-1 was increased,expression levels of iNOS CD11b,CD206 and Arg1 were significantly increased,and the neuronal apoptosis was increased.Notch1,p21 and Hes1 mRNA and protein levels were significantly increased(all P<0.05).Compared with TBI+NC agomir group,expression of miR-145 in hippocampus of mice in TBI+miR-145 agomir group was significantly increased,and neurological damage was reduced.Percentage of Tregs in CD4+T cell population in brain tissue was significantly increased,expressions of pro-inflammatory cytokines IL-1β,IL-6,and TNF-α were decreased,while anti-inflammatory cytokines IL-4,IL-10 and TGF-β were significantly increased in hippocampus.The number of activated microglia/macrophage IBA-1 was significantly decreased,expression levels of iNOS and CD11b were decreased,while expression levels of CD206 and Arg1 were significantly increased.mRNA and protein levels of Notch1,p21 and Hes1 were significantly reduced(all P<0.05).Conclusion:Overexpression of miR-145 promotes M2 polarization of microglia to regulate post-traumatic neuroinflammatory response and improve behavioral dysfunction by increasing Treg level,which may be mediated by Notch signaling pathway.
