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脑梗死小鼠中与细胞焦亡相关基因 Casp8、Gsdmd 和 Trem2 的研究

Study on pyroptosis-related genes Casp8, Gsdmd and Trem2 in mice with cerebral infarction.

机构信息

Department of Neurology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.

The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.

出版信息

PeerJ. 2024 Feb 9;12:e16818. doi: 10.7717/peerj.16818. eCollection 2024.

DOI:10.7717/peerj.16818
PMID:38348100
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10860548/
Abstract

OBJECTIVE

Cerebral infarction is the main cause of death in patients with cerebrovascular diseases. Our research aimed to screen and validate pyroptosis-related genes in cerebral infarction for the targeted therapy of cerebral infarction.

METHODS AND RESULTS

A total of 1,517 differentially expressed genes (DEGs) were obtained by DESeq2 software analysis. Gene set enrichment analysis results indicated that genes of middle cerebral artery occlusion (MCAO) mice aged 3 months and 18 months were enriched in pyroptosis, respectively. Differentially expressed pyroptosis-related genes (including Aim2, Casp8, Gsdmd, Naip2, Naip5, Naip6 and Trem2) were obtained through intersection of DEGs and genes from pyroptosis Gene Ontology Term (GO:0070269), and they were up-regulated in the brain tissues of MCAO mice in GSE137482. In addition, Casp8, Gsdmd, and Trem2 were verified to be significantly up-regulated in MCAO mice in GSE93376. The evaluation of neurologic function and triphenyltetrazolium chloride staining showed that the MCAO mouse models were successfully constructed. Meanwhile, the expressions of TNF-, pyroptosis-related proteins, Casp8, Gsdmd and Trem2 in MCAO mice were significantly up-regulated. We selected Trem2 for subsequent functional analysis. OGD treatment of BV2 cell significantly upregulated the expressions of Trem2. Subsequent downregulation of Trem2 expression in OGD-BV2 cells further increased the level of pyroptosis. Therefore, Trem2 is a protective factor regulating pyroptosis, thus influencing the progression of cerebral infarction.

CONCLUSIONS

Casp8, Gsdmd and Trem2 can regulate pyroptosis, thus affecting cerebral infarction.

摘要

目的

脑梗死是脑血管病患者死亡的主要原因。我们的研究旨在筛选和验证脑梗死中的细胞焦亡相关基因，为脑梗死的靶向治疗提供依据。

方法和结果

通过 DESeq2 软件分析获得了 1517 个差异表达基因（DEGs）。基因集富集分析结果表明，3 月龄和 18 月龄大脑中动脉闭塞（MCAO）小鼠的基因分别富集在细胞焦亡中。通过差异表达的细胞焦亡相关基因（包括 Aim2、Casp8、Gsdmd、Naip2、Naip5、Naip6 和 Trem2）与细胞焦亡基因本体论术语（GO：0070269）的 DEGs 取交集，获得差异表达的细胞焦亡相关基因，这些基因在 GSE137482 中的 MCAO 小鼠脑组织中呈上调表达。此外，在 GSE93376 中验证 Casp8、Gsdmd 和 Trem2 在 MCAO 小鼠中呈显著上调表达。神经功能评估和氯化三苯基四氮唑染色表明成功构建了 MCAO 小鼠模型。同时，MCAO 小鼠中 TNF-α、细胞焦亡相关蛋白、Casp8、Gsdmd 和 Trem2 的表达均显著上调。我们选择 Trem2 进行后续功能分析。OGD 处理 BV2 细胞可显著上调 Trem2 的表达。随后下调 OGD-BV2 细胞中的 Trem2 表达进一步增加了细胞焦亡水平。因此，Trem2 是调节细胞焦亡的保护因子，从而影响脑梗死的进展。

结论

Casp8、Gsdmd 和 Trem2 可调节细胞焦亡，从而影响脑梗死。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1af/10860548/15afc9bf56df/peerj-12-16818-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1af/10860548/15afc9bf56df/peerj-12-16818-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1af/10860548/c3f2da7e19f0/peerj-12-16818-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1af/10860548/15afc9bf56df/peerj-12-16818-g007.jpg

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