Protective effect of EGR1 on neuronal cell injury in ischemic stroke via AMPK/Nrf2 pathway
10.13431/j.cnki.immunol.j.20250069
- VernacularTitle:EGR1通过AMPK/Nrf2通路对缺血性卒中神经细胞损伤的保护作用
- Author:
Tingyu ZHANG
1
;
Jiaqi CHENG
;
Yushi TIAN
;
Ying HAI
Author Information
1. 辽宁中医药大学针灸推拿学院,沈阳 110847
- Publication Type:Journal Article
- Keywords:
ischemic stroke;
Mendel randomization;
genetic susceptibility;
differentially expressed genes;
EGR1
- From:
Immunological Journal
2025;41(7):476-482
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the mechanism by which the early growth response protein 1(EGR1)/AMP-activated protein kinase(AMPK)/nuclear factor erythroid 2-related factor 2(Nrf2)pathway improves Neuro-2a cell injury via Mendelian randomization(MR),bioinformatics and in vitro models of ischemic stroke(IS).Methods The blood proteins associated with genetic susceptibility to IS were identified based on MR analysis.Then,the GSE22255 dataset was comprehensively analyzed,including GSEA,immunoinfiltration and differential expression analysis.The transcription factors closely related to the occurrence and development of IS were identified after joint analysis with MR results,and the biological functions of key genes were further verified by in vitro experiments.Results A total of 712 proteins related to IS susceptibility were identified by MR analysis.A total of 2357 differentially expressed genes were identified from the GSE22255 dataset,and 75 intersection genes and 34 transcription factors were identified after combined analysis with MR results.In vitro experiments showed that knockdown of EGR1 expression could significantly inhibit oxygen-glucose deprivation/reperfusion(OGD/R)-induced Neuro-2a cell damage,and the mechanism might be related to the up-regulation of p-AMPK and Nrf2 protein expression.Conclusion This study integrates MR analysis,transcriptomics and in vitro experiments to reveal the potential role of 75 IS susceptibility genes and transcription factor EGR1 in the pathogenesis of IS,which provides theoretical basis for the development of therapeutic drugs for IS.
