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Integrated Analysis of Expression Profile Based on Differentially Expressed Genes in Middle Cerebral Artery Occlusion Animal Models.

ABSTRACT: Stroke is one of the most common causes of death, only second to heart disease. Molecular investigations about stroke are in acute shortage nowadays. This study is intended to explore a gene expression profile after brain ischemia reperfusion. Meta-analysis, differential expression analysis, and integrated analysis were employed on an eight microarray series. We explored the functions and pathways of target genes in gene ontology (GO) enrichment analysis and constructed a protein-protein interaction network. Meta-analysis identified 360 differentially expressed genes (DEGs) for Mus musculus and 255 for Rattus norvegicus. Differential expression analysis identified 44 DEGs for Mus musculus and 21 for Rattus norvegicus. Timp1 and Lcn2 were overexpressed in both species. The cytokine-cytokine receptor interaction and chemokine signaling pathway were highly enriched for the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. We have exhibited a global view of the potential molecular differences between middle cerebral artery occlusion (MCAO) animal model and sham for Mus musculus or Rattus norvegicus, including the biological process and enriched pathways in DEGs. This research helps contribute to a clearer understanding of the inflammation process and accurate identification of ischemic infarction stages, which might be transformed into a therapeutic approach.

SUBMITTER: Zhou H

PROVIDER: S-EPMC4881595 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Integrated Analysis of Expression Profile Based on Differentially Expressed Genes in Middle Cerebral Artery Occlusion Animal Models.

Zhou Huaqiang H Qiu Zeting Z Gao Shaowei S Chen Qinchang Q Li Si S Tan Wulin W Liu Xiaochen X Wang Zhongxing Z

International journal of molecular sciences 20160520 5

Stroke is one of the most common causes of death, only second to heart disease. Molecular investigations about stroke are in acute shortage nowadays. This study is intended to explore a gene expression profile after brain ischemia reperfusion. Meta-analysis, differential expression analysis, and integrated analysis were employed on an eight microarray series. We explored the functions and pathways of target genes in gene ontology (GO) enrichment analysis and constructed a protein-protein interac ...[more]

PMID: 27213359

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Project description:BackgroundRetinoic acid is a major metabolite of vitamin A and exerts beneficial effects including anti-oxidant and anti-inflammatory activities in neurons. The ubiquitin-proteasome system is an important biological system that regulates cell survival. Ubiquitination regulates protein degradation and plays an important role in oxidative stress. Deubiquitinating enzymes cleave ubiquitin from proteins and control ubiquitination-induced degradation. We detected decreases in ubiquitin carboxy-terminal hydrolase L1, ubiquitin thioesterase OTUB1, and proteasome subunit alpha types 1 and 3 in cerebral ischemic damage. In this study, we investigated whether retinoic acid regulates the expression of deubiquitinating enzymes ubiquitin carboxy-terminal hydrolase L1, ubiquitin thioesterase OTUB1, and proteasome subunit alpha types 1 and 3 in cerebral ischemic injury. Right middle cerebral artery occlusion (MCAO) was performed to induce cerebral ischemic damage in male rats. Retinoic acid (5 mg/kg) or vehicle was intraperitoneally injected every day from 4 days before surgery. Neurological behavioral tests were performed 24 h after MCAO, and right cerebral cortical tissues were collected.ResultsMCAO damage caused neurological behavioral dysfunction, and retinoic acid alleviated these deficits. The identified proteins decreased in MCAO animals with vehicle, while retinoic acid treatment attenuated these decreases. The results of proteomic study were confirmed by a reverse transcription-PCR technique. Expressions of ubiquitin carboxy-terminal hydrolase L1, ubiquitin thioesterase OTUB1, and proteasome subunit alpha types 1 and 3 were decreased in MCAO animals treated with vehicle. Retinoic acid treatment alleviated these MCAO-induced reductions. The ubiquitin-proteasome system plays an essential role in maintaining cell function and preserving cell shape against ischemic damage.ConclusionsThese findings suggest that retinoic acid regulates ubiquitin- and proteasome-related proteins including ubiquitin carboxy-terminal hydrolase L1, ubiquitin thioesterase OTUB1, and proteasome subunit alpha types 1 and 3 in a brain ischemia model. Changes in these proteins are involved in the neuroprotective effects of retinoic acid.

Dataset Information

Integrated Analysis of Expression Profile Based on Differentially Expressed Genes in Middle Cerebral Artery Occlusion Animal Models.

Publications

Integrated Analysis of Expression Profile Based on Differentially Expressed Genes in Middle Cerebral Artery Occlusion Animal Models.

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