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Identification of TIMP1 as an inflammatory biomarker associated with temporal lobe epilepsy based on integrated bioinformatics and experimental analyses

BACKGROUND: Epilepsy is the second most prevalent neurological disease. Although there are many antiseizure drugs, approximately 30% of cases are refractory to treatment. Temporal lobe epilepsy (TLE) is the most common epilepsy subtype, and previous studies have reported that hippocampal inflammatio...

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Autores principales: He, Ya, Zhang, Hongxia, Ma, Limin, Li, Jingang, Wang, Fei, Zhou, Hui, Zhang, Guangliang, Wen, Yuetao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10294353/
https://www.ncbi.nlm.nih.gov/pubmed/37365625
http://dx.doi.org/10.1186/s12974-023-02837-3
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author He, Ya
Zhang, Hongxia
Ma, Limin
Li, Jingang
Wang, Fei
Zhou, Hui
Zhang, Guangliang
Wen, Yuetao
author_facet He, Ya
Zhang, Hongxia
Ma, Limin
Li, Jingang
Wang, Fei
Zhou, Hui
Zhang, Guangliang
Wen, Yuetao
author_sort He, Ya
collection PubMed
description BACKGROUND: Epilepsy is the second most prevalent neurological disease. Although there are many antiseizure drugs, approximately 30% of cases are refractory to treatment. Temporal lobe epilepsy (TLE) is the most common epilepsy subtype, and previous studies have reported that hippocampal inflammation is an important mechanism associated with the occurrence and development of TLE. However, the inflammatory biomarkers associated with TLE are not well defined. METHODS: In our study, we merged human hippocampus datasets (GSE48350 and GSE63808) through batch correction and generally verified the diagnostic roles of inflammation-related genes (IRGs) and subtype classification according to IRGs in epilepsy through differential expression, random forest, support vector machine, nomogram, subtype classification, enrichment, protein‒protein interaction, immune cell infiltration, and immune function analyses. Finally, we detected the location and expression of inhibitor of metalloproteinase-1 (TIMP1) in epileptic patients and kainic acid-induced epileptic mice. RESULTS: According to the bioinformatics analysis, we identified TIMP1 as the most significant IRG associated with TLE, and we found that TIMP1 was mainly located in cortical neurons and scantly expressed in cortical gliocytes by immunofluorescence staining. We detected decreased expression of TIMP1 by quantitative real-time polymerase chain reaction and western blotting. CONCLUSION: TIMP1, the most significant IRG associated with TLE, might be a novel and promising biomarker to study the mechanism of epilepsy and guide the discovery of new drugs for its treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-023-02837-3.
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spelling pubmed-102943532023-06-28 Identification of TIMP1 as an inflammatory biomarker associated with temporal lobe epilepsy based on integrated bioinformatics and experimental analyses He, Ya Zhang, Hongxia Ma, Limin Li, Jingang Wang, Fei Zhou, Hui Zhang, Guangliang Wen, Yuetao J Neuroinflammation Research BACKGROUND: Epilepsy is the second most prevalent neurological disease. Although there are many antiseizure drugs, approximately 30% of cases are refractory to treatment. Temporal lobe epilepsy (TLE) is the most common epilepsy subtype, and previous studies have reported that hippocampal inflammation is an important mechanism associated with the occurrence and development of TLE. However, the inflammatory biomarkers associated with TLE are not well defined. METHODS: In our study, we merged human hippocampus datasets (GSE48350 and GSE63808) through batch correction and generally verified the diagnostic roles of inflammation-related genes (IRGs) and subtype classification according to IRGs in epilepsy through differential expression, random forest, support vector machine, nomogram, subtype classification, enrichment, protein‒protein interaction, immune cell infiltration, and immune function analyses. Finally, we detected the location and expression of inhibitor of metalloproteinase-1 (TIMP1) in epileptic patients and kainic acid-induced epileptic mice. RESULTS: According to the bioinformatics analysis, we identified TIMP1 as the most significant IRG associated with TLE, and we found that TIMP1 was mainly located in cortical neurons and scantly expressed in cortical gliocytes by immunofluorescence staining. We detected decreased expression of TIMP1 by quantitative real-time polymerase chain reaction and western blotting. CONCLUSION: TIMP1, the most significant IRG associated with TLE, might be a novel and promising biomarker to study the mechanism of epilepsy and guide the discovery of new drugs for its treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-023-02837-3. BioMed Central 2023-06-26 /pmc/articles/PMC10294353/ /pubmed/37365625 http://dx.doi.org/10.1186/s12974-023-02837-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
He, Ya
Zhang, Hongxia
Ma, Limin
Li, Jingang
Wang, Fei
Zhou, Hui
Zhang, Guangliang
Wen, Yuetao
Identification of TIMP1 as an inflammatory biomarker associated with temporal lobe epilepsy based on integrated bioinformatics and experimental analyses
title Identification of TIMP1 as an inflammatory biomarker associated with temporal lobe epilepsy based on integrated bioinformatics and experimental analyses
title_full Identification of TIMP1 as an inflammatory biomarker associated with temporal lobe epilepsy based on integrated bioinformatics and experimental analyses
title_fullStr Identification of TIMP1 as an inflammatory biomarker associated with temporal lobe epilepsy based on integrated bioinformatics and experimental analyses
title_full_unstemmed Identification of TIMP1 as an inflammatory biomarker associated with temporal lobe epilepsy based on integrated bioinformatics and experimental analyses
title_short Identification of TIMP1 as an inflammatory biomarker associated with temporal lobe epilepsy based on integrated bioinformatics and experimental analyses
title_sort identification of timp1 as an inflammatory biomarker associated with temporal lobe epilepsy based on integrated bioinformatics and experimental analyses
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10294353/
https://www.ncbi.nlm.nih.gov/pubmed/37365625
http://dx.doi.org/10.1186/s12974-023-02837-3
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