{"title":"ANXA2敲低通过抑制toll样受体(TLR)通路抑制氧化应激和焦亡减轻癫痫。","authors":"Fen Wang , Jiaomei Jiang, Ting Xu, Yongmin Ding","doi":"10.1016/j.cellsig.2025.112140","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>Epilepsy (EP), characterized by recurrent unprovoked seizures, affects over 50 million individuals globally and imposes substantial socioeconomic and healthcare burdens. We aim to investigate the mechanism by which Annexin A2 (ANXA2) regulates epileptic seizures.</div></div><div><h3>Methods</h3><div>Differentially expressed genes related to EP were identified from GSE73878 and GSE88992 datasets. ANXA2 was identified as a key hub gene through protein-protein interaction (PPI) network analysis. The oxidative stress indicators and inflammatory cytokines were measured by enzyme-linked immunosorbent assay. The proteins related to pyroptosis and pathways were detected by western blot. The role of ANXA2 in kainic acid (KA)-induced hippocampal neurons was evaluated by detecting viability and apoptosis. EP in rats was induced by lithium chloride combined with pilocarpine. The effect of ANXA2 on EP rats was assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling, hematoxylin and eosin, and Nissl staining.</div></div><div><h3>Results</h3><div>ANXA2 was identified as a key hub gene related to EP with high predictive value, which was upregulated in KA-induced hippocampal neurons. In vitro, ANXA2 knockdown inhibited oxidative stress, pyroptosis, and apoptosis, while promoting cell viability. Additionally, ANXA2 knockdown reduced oxidative stress, pyroptosis, and epileptic seizures in EP rats. Moreover, ANXA2 knockdown inhibited the toll-like receptor (TLR) pathway in EP rats. Specifically, the activation of the TLR pathway reversed the protective effect of ANXA2 knockdown on both KA-induced hippocampal neurons and EP rats.</div></div><div><h3>Conclusion</h3><div>ANXA2 knockdown mitigates EP by reducing oxidative stress and pyroptosis via suppressing the TLR pathway, highlighting its potential as a therapeutic target for EP treatment.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"136 ","pages":"Article 112140"},"PeriodicalIF":3.7000,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"ANXA2 knockdown inhibits oxidative stress and pyroptosis to alleviate epilepsy by suppressing the toll-like receptor (TLR) pathway\",\"authors\":\"Fen Wang , Jiaomei Jiang, Ting Xu, Yongmin Ding\",\"doi\":\"10.1016/j.cellsig.2025.112140\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><div>Epilepsy (EP), characterized by recurrent unprovoked seizures, affects over 50 million individuals globally and imposes substantial socioeconomic and healthcare burdens. We aim to investigate the mechanism by which Annexin A2 (ANXA2) regulates epileptic seizures.</div></div><div><h3>Methods</h3><div>Differentially expressed genes related to EP were identified from GSE73878 and GSE88992 datasets. ANXA2 was identified as a key hub gene through protein-protein interaction (PPI) network analysis. The oxidative stress indicators and inflammatory cytokines were measured by enzyme-linked immunosorbent assay. The proteins related to pyroptosis and pathways were detected by western blot. The role of ANXA2 in kainic acid (KA)-induced hippocampal neurons was evaluated by detecting viability and apoptosis. EP in rats was induced by lithium chloride combined with pilocarpine. The effect of ANXA2 on EP rats was assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling, hematoxylin and eosin, and Nissl staining.</div></div><div><h3>Results</h3><div>ANXA2 was identified as a key hub gene related to EP with high predictive value, which was upregulated in KA-induced hippocampal neurons. In vitro, ANXA2 knockdown inhibited oxidative stress, pyroptosis, and apoptosis, while promoting cell viability. Additionally, ANXA2 knockdown reduced oxidative stress, pyroptosis, and epileptic seizures in EP rats. Moreover, ANXA2 knockdown inhibited the toll-like receptor (TLR) pathway in EP rats. Specifically, the activation of the TLR pathway reversed the protective effect of ANXA2 knockdown on both KA-induced hippocampal neurons and EP rats.</div></div><div><h3>Conclusion</h3><div>ANXA2 knockdown mitigates EP by reducing oxidative stress and pyroptosis via suppressing the TLR pathway, highlighting its potential as a therapeutic target for EP treatment.</div></div>\",\"PeriodicalId\":9902,\"journal\":{\"name\":\"Cellular signalling\",\"volume\":\"136 \",\"pages\":\"Article 112140\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2025-09-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cellular signalling\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0898656825005558\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular signalling","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0898656825005558","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
ANXA2 knockdown inhibits oxidative stress and pyroptosis to alleviate epilepsy by suppressing the toll-like receptor (TLR) pathway
Objective
Epilepsy (EP), characterized by recurrent unprovoked seizures, affects over 50 million individuals globally and imposes substantial socioeconomic and healthcare burdens. We aim to investigate the mechanism by which Annexin A2 (ANXA2) regulates epileptic seizures.
Methods
Differentially expressed genes related to EP were identified from GSE73878 and GSE88992 datasets. ANXA2 was identified as a key hub gene through protein-protein interaction (PPI) network analysis. The oxidative stress indicators and inflammatory cytokines were measured by enzyme-linked immunosorbent assay. The proteins related to pyroptosis and pathways were detected by western blot. The role of ANXA2 in kainic acid (KA)-induced hippocampal neurons was evaluated by detecting viability and apoptosis. EP in rats was induced by lithium chloride combined with pilocarpine. The effect of ANXA2 on EP rats was assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling, hematoxylin and eosin, and Nissl staining.
Results
ANXA2 was identified as a key hub gene related to EP with high predictive value, which was upregulated in KA-induced hippocampal neurons. In vitro, ANXA2 knockdown inhibited oxidative stress, pyroptosis, and apoptosis, while promoting cell viability. Additionally, ANXA2 knockdown reduced oxidative stress, pyroptosis, and epileptic seizures in EP rats. Moreover, ANXA2 knockdown inhibited the toll-like receptor (TLR) pathway in EP rats. Specifically, the activation of the TLR pathway reversed the protective effect of ANXA2 knockdown on both KA-induced hippocampal neurons and EP rats.
Conclusion
ANXA2 knockdown mitigates EP by reducing oxidative stress and pyroptosis via suppressing the TLR pathway, highlighting its potential as a therapeutic target for EP treatment.
期刊介绍:
Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo.
Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.