Re-Exploring the Inflammation-Related Core Genes and Modules in Cerebral Ischemia.
Brain ischemia
Inflammation
Reperfusion injury
Thrombo-inflammation
Journal
Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963
Informations de publication
Date de publication:
Jun 2023
Jun 2023
Historique:
received:
20
03
2022
accepted:
16
02
2023
medline:
25
4
2023
pubmed:
4
3
2023
entrez:
3
3
2023
Statut:
ppublish
Résumé
The genetic transcription profile of brain ischemic and reperfusion injury remains elusive. To address this, we used an integrative analysis approach including differentially expressed gene (DEG) analysis, weighted-gene co-expression network analysis (WGCNA), and pathway and biological process analysis to analyze data from the microarray studies of nine mice and five rats after middle cerebral artery occlusion (MCAO) and six primary cell transcriptional datasets in the Gene Expression Omnibus (GEO). (1) We identified 58 upregulated DEGs with more than 2-fold increase, and adj. p < 0.05 in mouse datasets. Among them, Atf3, Timp1, Cd14, Lgals3, Hmox1, Ccl2, Emp1, Ch25h, Hspb1, Adamts1, Cd44, Icam1, Anxa2, Rgs1, and Vim showed significant increases in both mouse and rat datasets. (2) Ischemic treatment and reperfusion time were the main confounding factors in gene profile changes, while sampling site and ischemic time were not. (3) WGCNA identified a reperfusion-time irrelevant and inflammation-related module and a reperfusion-time relevant and thrombo-inflammation related module. Astrocytes and microglia were the main contributors of the gene changes in these two modules. (4) Forty-four module core hub genes were identified. We validated the expression of unreported stroke-associated core hubs or human stroke-associated core hubs. Zfp36 mRNA was upregulated in permanent MCAO; Rhoj, Nfkbiz, Ms4a6d, Serpina3n, Adamts-1, Lgals3, and Spp1 mRNAs were upregulated in both transient MCAO and permanent MCAO; and NFKBIZ, ZFP3636, and MAFF proteins, unreported core hubs implicated in negative regulation of inflammation, were upregulated in permanent MCAO, but not in transient MCAO. Collectively, these results expand our knowledge of the genetic profile involved in brain ischemia and reperfusion, highlighting the crucial role of inflammatory disequilibrium in brain ischemia.
Identifiants
pubmed: 36867343
doi: 10.1007/s12035-023-03275-1
pii: 10.1007/s12035-023-03275-1
doi:
Substances chimiques
Galectin 3
0
RNA, Messenger
0
RHOJ protein, human
EC 3.6.1.-
rho GTP-Binding Proteins
EC 3.6.5.2
Nfkbiz protein, mouse
0
Adaptor Proteins, Signal Transducing
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3439-3451Subventions
Organisme : National Key R&D Program of China
ID : 2019YFC0120000
Organisme : National Key R&D Program of China
ID : 2018YFC1312300
Organisme : National Natural Science Foundation of China
ID : NSFC: 82071385
Organisme : Key Research and Development Project of Shandong
ID : 2019JZZY021010
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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