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Relationship Between the Pyroptosis Pathway and Epilepsy: A Bioinformatic Analysis
PURPOSE: This study aimed to analyse the correlation between the pyroptosis pathway and epilepsy using bioinformatics analysis technology. We analyzed the expression of gasdermin D (GSDMD) and gasdermin E (GSDME), the key molecules of pyroptosis, in kainic acid-induced epileptic mice. METHODS: Weigh...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795950/ https://www.ncbi.nlm.nih.gov/pubmed/35095728 http://dx.doi.org/10.3389/fneur.2021.782739 |
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author | Xia, Lu Liu, Lu Wang, Qiang Ding, Jing Wang, Xin |
author_facet | Xia, Lu Liu, Lu Wang, Qiang Ding, Jing Wang, Xin |
author_sort | Xia, Lu |
collection | PubMed |
description | PURPOSE: This study aimed to analyse the correlation between the pyroptosis pathway and epilepsy using bioinformatics analysis technology. We analyzed the expression of gasdermin D (GSDMD) and gasdermin E (GSDME), the key molecules of pyroptosis, in kainic acid-induced epileptic mice. METHODS: Weighted gene co-expression network analysis (WGCNA) was used to construct a signed co-expression network from expression data to screen gene sets closely related to epilepsy. The correlation between the module and epilepsy was verified through module conservative analysis, gene ontology (GO) annotation analysis, and correlation analysis with known epilepsy genes. We obtained currently recognized pyroptosis-related molecules through literature review, and correlation analysis was used to evaluate their correlation with epilepsy. Differentially expressed gene (DEG) analysis was used to analyse expression changes of pyroptosis-related molecules at the transcriptome level, compared to the sham group. We subsequently established a kainic acid-induced status epilepticus (SE) model in mice and validated the mRNA and protein expression of GSDMD and GSDME, the key molecules of pyroptosis, by quantitative reverse transcription PCR (qRT-PCR) and western blotting (WB). RESULTS: Using WGCNA, module conservative analysis, and correlation analysis with known epilepsy genes, we screened out a module (a gene set of interest) closely related to epilepsy that was prominently enriched in immune and inflammatory-related biological processes. Correlation analysis results suggest that pyroptosis-related molecules are closely related to this module, but have no obvious correlation with others. DEG analysis of molecules associated with pyroptosis suggests that most of the pyroptosis-related molecules had significantly increased expression after SE, such as IL1b, Casp1, Casp4, Pycard, Gsdmd, Nlrp3, Aim2, Mefv, Tlr2, Tlr3, and Tlr4. qRT-PCR and WB analysis confirmed that the mRNA and protein levels of GSDMD in the mouse hippocampus were significantly upregulated after SE. The mRNA expression of GSDME was not different between the epilepsy group and sham group. However, the WB results showed that the expression of full-length GSDME was decreased and GSDME-N-terminus were significantly increased after SE. CONCLUSIONS: Our study highlights that the pyroptosis pathway may be closely related to epilepsy. GSDMD and GSDME, the key executive molecules of pyroptosis, will help to understand the pathogenesis of epilepsy and aid in discovering new targets for anti-epileptic drug treatments. |
format | Online Article Text |
id | pubmed-8795950 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87959502022-01-29 Relationship Between the Pyroptosis Pathway and Epilepsy: A Bioinformatic Analysis Xia, Lu Liu, Lu Wang, Qiang Ding, Jing Wang, Xin Front Neurol Neurology PURPOSE: This study aimed to analyse the correlation between the pyroptosis pathway and epilepsy using bioinformatics analysis technology. We analyzed the expression of gasdermin D (GSDMD) and gasdermin E (GSDME), the key molecules of pyroptosis, in kainic acid-induced epileptic mice. METHODS: Weighted gene co-expression network analysis (WGCNA) was used to construct a signed co-expression network from expression data to screen gene sets closely related to epilepsy. The correlation between the module and epilepsy was verified through module conservative analysis, gene ontology (GO) annotation analysis, and correlation analysis with known epilepsy genes. We obtained currently recognized pyroptosis-related molecules through literature review, and correlation analysis was used to evaluate their correlation with epilepsy. Differentially expressed gene (DEG) analysis was used to analyse expression changes of pyroptosis-related molecules at the transcriptome level, compared to the sham group. We subsequently established a kainic acid-induced status epilepticus (SE) model in mice and validated the mRNA and protein expression of GSDMD and GSDME, the key molecules of pyroptosis, by quantitative reverse transcription PCR (qRT-PCR) and western blotting (WB). RESULTS: Using WGCNA, module conservative analysis, and correlation analysis with known epilepsy genes, we screened out a module (a gene set of interest) closely related to epilepsy that was prominently enriched in immune and inflammatory-related biological processes. Correlation analysis results suggest that pyroptosis-related molecules are closely related to this module, but have no obvious correlation with others. DEG analysis of molecules associated with pyroptosis suggests that most of the pyroptosis-related molecules had significantly increased expression after SE, such as IL1b, Casp1, Casp4, Pycard, Gsdmd, Nlrp3, Aim2, Mefv, Tlr2, Tlr3, and Tlr4. qRT-PCR and WB analysis confirmed that the mRNA and protein levels of GSDMD in the mouse hippocampus were significantly upregulated after SE. The mRNA expression of GSDME was not different between the epilepsy group and sham group. However, the WB results showed that the expression of full-length GSDME was decreased and GSDME-N-terminus were significantly increased after SE. CONCLUSIONS: Our study highlights that the pyroptosis pathway may be closely related to epilepsy. GSDMD and GSDME, the key executive molecules of pyroptosis, will help to understand the pathogenesis of epilepsy and aid in discovering new targets for anti-epileptic drug treatments. Frontiers Media S.A. 2022-01-14 /pmc/articles/PMC8795950/ /pubmed/35095728 http://dx.doi.org/10.3389/fneur.2021.782739 Text en Copyright © 2022 Xia, Liu, Wang, Ding and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neurology Xia, Lu Liu, Lu Wang, Qiang Ding, Jing Wang, Xin Relationship Between the Pyroptosis Pathway and Epilepsy: A Bioinformatic Analysis |
title | Relationship Between the Pyroptosis Pathway and Epilepsy: A Bioinformatic Analysis |
title_full | Relationship Between the Pyroptosis Pathway and Epilepsy: A Bioinformatic Analysis |
title_fullStr | Relationship Between the Pyroptosis Pathway and Epilepsy: A Bioinformatic Analysis |
title_full_unstemmed | Relationship Between the Pyroptosis Pathway and Epilepsy: A Bioinformatic Analysis |
title_short | Relationship Between the Pyroptosis Pathway and Epilepsy: A Bioinformatic Analysis |
title_sort | relationship between the pyroptosis pathway and epilepsy: a bioinformatic analysis |
topic | Neurology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795950/ https://www.ncbi.nlm.nih.gov/pubmed/35095728 http://dx.doi.org/10.3389/fneur.2021.782739 |
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