Identifying the Involvement of Pro-Inflammatory Signal in Hippocampal Gene Expression Changes after Experimental Ischemia: Transcriptome-Wide Analysis.
Galina T ShishkinaNatalia V GulyaevaDmitriy A LanshakovTatyana S KalininaMikhail V OnufrievYulia V MoiseevaEkaterina V SukharevaVladimir N BabenkoNikolay N DygaloPublished in: Biomedicines (2021)
Acute cerebral ischemia induces distant inflammation in the hippocampus; however, molecular mechanisms of this phenomenon remain obscure. Here, hippocampal gene expression profiles were compared in two experimental paradigms in rats: middle cerebral artery occlusion (MCAO) and intracerebral administration of lipopolysaccharide (LPS). The main finding is that 10 genes ( Clec5a, CD14, Fgr, Hck, Anxa1, Lgals3, Irf1, Lbp, Ptx3, Serping1 ) may represent key molecular links underlying acute activation of immune cells in the hippocampus in response to experimental ischemia. Functional annotation clustering revealed that these genes built the same clusters related to innate immunity/immunity/innate immune response in all MCAO differentially expressed genes and responded to the direct pro-inflammatory stimulus group. The gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses also indicate that LPS-responding genes were the most abundant among the genes related to "positive regulation of tumor necrosis factor biosynthetic process", "cell adhesion", "TNF signaling pathway", and "phagosome" as compared with non-responding ones. In contrast, positive and negative "regulation of cell proliferation" and "HIF-1 signaling pathway" mostly enriched with genes that did not respond to LPS. These results contribute to understanding genomic mechanisms of the impact of immune/inflammatory activation on expression of hippocampal genes after focal brain ischemia.
Keyphrases
- genome wide
- genome wide identification
- cerebral ischemia
- immune response
- gene expression
- signaling pathway
- bioinformatics analysis
- dna methylation
- cell proliferation
- inflammatory response
- middle cerebral artery
- subarachnoid hemorrhage
- copy number
- single cell
- rheumatoid arthritis
- liver failure
- oxidative stress
- brain injury
- magnetic resonance
- transcription factor
- pi k akt
- multiple sclerosis
- rna seq
- drug induced
- computed tomography
- cell adhesion
- respiratory failure
- internal carotid artery
- intensive care unit
- endothelial cells
- cell cycle
- extracorporeal membrane oxygenation
- long non coding rna
- hepatitis b virus
- aortic dissection
- temporal lobe epilepsy
- single molecule