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。

IF 3.7 2区 生物学 Q2 CELL BIOLOGY
Fen Wang , Jiaomei Jiang, Ting Xu, Yongmin Ding
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引用次数: 0

摘要

目的:癫痫(EP)以反复发作为特征,影响着全球5000多万人,并造成了巨大的社会经济和医疗负担。我们的目的是研究膜联蛋白A2 (ANXA2)调控癫痫发作的机制。方法:从GSE73878和GSE88992数据集中鉴定EP相关差异表达基因。通过蛋白相互作用(PPI)网络分析,确定ANXA2为关键枢纽基因。采用酶联免疫吸附法测定氧化应激指标和炎症因子。western blot检测焦亡相关蛋白及相关通路。通过检测kainic acid (KA)诱导海马神经元的活性和凋亡来评估ANXA2在海马神经元中的作用。氯化锂联合匹罗卡品诱导大鼠EP。采用末端脱氧核苷酸转移酶dUTP镍端标记法、苏木精和伊红染色法、尼氏染色法评价ANXA2对EP大鼠的影响。结果:ANXA2在ka诱导的海马神经元中表达上调,是与EP相关的关键枢纽基因,具有较高的预测价值。在体外,ANXA2敲低抑制氧化应激、焦亡和凋亡,同时促进细胞活力。此外,ANXA2敲低可降低EP大鼠的氧化应激、焦亡和癫痫发作。此外,ANXA2敲低可抑制EP大鼠toll样受体(TLR)通路。具体来说,TLR通路的激活逆转了ANXA2敲低对ka诱导的海马神经元和EP大鼠的保护作用。结论:ANXA2敲低可通过抑制TLR通路减少氧化应激和焦亡,从而减轻EP,突出其作为EP治疗靶点的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

ANXA2 knockdown inhibits oxidative stress and pyroptosis to alleviate epilepsy by suppressing the toll-like receptor (TLR) pathway

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.
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来源期刊
Cellular signalling
Cellular signalling 生物-细胞生物学
CiteScore
8.40
自引率
0.00%
发文量
250
审稿时长
27 days
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.
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