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Bioinformatics and experimental analyses of glutamate receptor and its targets genes in myocardial and cerebral ischemia
BACKGROUND: There is a mutual hemodynamic and pathophysiological basis between the heart and brain. Glutamate (GLU) signaling plays an important role in the process of myocardial ischemia (MI) and ischemic stroke (IS). To further explore the common protective mechanism after cardiac and cerebral isc...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10239159/ https://www.ncbi.nlm.nih.gov/pubmed/37268894 http://dx.doi.org/10.1186/s12864-023-09408-z |
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author | Liao, Wei He, Chunming Yang, Shaochun Zhou, Man Zeng, Chuan Luo, Muyun Yu, Junjian Hu, Shuo Duan, Yanyu Liu, Ziyou |
author_facet | Liao, Wei He, Chunming Yang, Shaochun Zhou, Man Zeng, Chuan Luo, Muyun Yu, Junjian Hu, Shuo Duan, Yanyu Liu, Ziyou |
author_sort | Liao, Wei |
collection | PubMed |
description | BACKGROUND: There is a mutual hemodynamic and pathophysiological basis between the heart and brain. Glutamate (GLU) signaling plays an important role in the process of myocardial ischemia (MI) and ischemic stroke (IS). To further explore the common protective mechanism after cardiac and cerebral ischemic injuries, the relationship between GLU receptor-related genes and MI and IS were analyzed. RESULTS: A total of 25 crosstalk genes were identified, which were mainly enriched in the Toll-like receptor signaling pathway, Th17 cell differentiation, and other signaling pathways. Protein-protein interaction analysis suggested that the top six genes with the most interactions with shared genes were IL6, TLR4, IL1B, SRC, TLR2, and CCL2. Immune infiltration analysis suggested that immune cells such as myeloid-derived suppressor cells and monocytes were highly expressed in the MI and IS data. Memory B cells and Th17 cells were expressed at low levels in the MI and IS data; molecular interaction network construction suggested that genes such as JUN, FOS, and PPARA were shared genes and transcription factors; FCGR2A was a shared gene of MI and IS as well as an immune gene. Least absolute shrinkage and selection operator logistic regression analysis identified nine hub genes: IL1B, FOS, JUN, FCGR2A, IL6, AKT1, DRD4, GLUD2, and SRC. Receiver operating characteristic analysis revealed that the area under the curve of these hub genes was > 65% in MI and IS for all seven genes except IL6 and DRD4. Furthermore, clinical blood samples and cellular models showed that the expression of relevant hub genes was consistent with the bioinformatics analysis. CONCLUSIONS: In this study, we found that the GLU receptor-related genes IL1B, FOS, JUN, FCGR2A, and SRC were expressed in MI and IS with the same trend, which can be used to predict the occurrence of cardiac and cerebral ischemic diseases and provide reliable biomarkers to further explore the co-protective mechanism after cardiac and cerebral ischemic injury. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-023-09408-z. |
format | Online Article Text |
id | pubmed-10239159 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-102391592023-06-04 Bioinformatics and experimental analyses of glutamate receptor and its targets genes in myocardial and cerebral ischemia Liao, Wei He, Chunming Yang, Shaochun Zhou, Man Zeng, Chuan Luo, Muyun Yu, Junjian Hu, Shuo Duan, Yanyu Liu, Ziyou BMC Genomics Research BACKGROUND: There is a mutual hemodynamic and pathophysiological basis between the heart and brain. Glutamate (GLU) signaling plays an important role in the process of myocardial ischemia (MI) and ischemic stroke (IS). To further explore the common protective mechanism after cardiac and cerebral ischemic injuries, the relationship between GLU receptor-related genes and MI and IS were analyzed. RESULTS: A total of 25 crosstalk genes were identified, which were mainly enriched in the Toll-like receptor signaling pathway, Th17 cell differentiation, and other signaling pathways. Protein-protein interaction analysis suggested that the top six genes with the most interactions with shared genes were IL6, TLR4, IL1B, SRC, TLR2, and CCL2. Immune infiltration analysis suggested that immune cells such as myeloid-derived suppressor cells and monocytes were highly expressed in the MI and IS data. Memory B cells and Th17 cells were expressed at low levels in the MI and IS data; molecular interaction network construction suggested that genes such as JUN, FOS, and PPARA were shared genes and transcription factors; FCGR2A was a shared gene of MI and IS as well as an immune gene. Least absolute shrinkage and selection operator logistic regression analysis identified nine hub genes: IL1B, FOS, JUN, FCGR2A, IL6, AKT1, DRD4, GLUD2, and SRC. Receiver operating characteristic analysis revealed that the area under the curve of these hub genes was > 65% in MI and IS for all seven genes except IL6 and DRD4. Furthermore, clinical blood samples and cellular models showed that the expression of relevant hub genes was consistent with the bioinformatics analysis. CONCLUSIONS: In this study, we found that the GLU receptor-related genes IL1B, FOS, JUN, FCGR2A, and SRC were expressed in MI and IS with the same trend, which can be used to predict the occurrence of cardiac and cerebral ischemic diseases and provide reliable biomarkers to further explore the co-protective mechanism after cardiac and cerebral ischemic injury. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-023-09408-z. BioMed Central 2023-06-02 /pmc/articles/PMC10239159/ /pubmed/37268894 http://dx.doi.org/10.1186/s12864-023-09408-z 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 Liao, Wei He, Chunming Yang, Shaochun Zhou, Man Zeng, Chuan Luo, Muyun Yu, Junjian Hu, Shuo Duan, Yanyu Liu, Ziyou Bioinformatics and experimental analyses of glutamate receptor and its targets genes in myocardial and cerebral ischemia |
title | Bioinformatics and experimental analyses of glutamate receptor and its targets genes in myocardial and cerebral ischemia |
title_full | Bioinformatics and experimental analyses of glutamate receptor and its targets genes in myocardial and cerebral ischemia |
title_fullStr | Bioinformatics and experimental analyses of glutamate receptor and its targets genes in myocardial and cerebral ischemia |
title_full_unstemmed | Bioinformatics and experimental analyses of glutamate receptor and its targets genes in myocardial and cerebral ischemia |
title_short | Bioinformatics and experimental analyses of glutamate receptor and its targets genes in myocardial and cerebral ischemia |
title_sort | bioinformatics and experimental analyses of glutamate receptor and its targets genes in myocardial and cerebral ischemia |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10239159/ https://www.ncbi.nlm.nih.gov/pubmed/37268894 http://dx.doi.org/10.1186/s12864-023-09408-z |
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