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SPP1/AnxA1/TIMP1 as Essential Genes Regulate the Inflammatory Response in the Acute Phase of Cerebral Ischemia-Reperfusion in Rats
BACKGROUND: Ischemic injury in stroke is followed by extensive neurovascular inflammation and changes in ischemic penumbra gene expression patterns. However, the key molecules involved in the inflammatory response during the acute phase of ischemic stroke remain unclear. METHODS: Gene expression pro...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9420928/ https://www.ncbi.nlm.nih.gov/pubmed/36046663 http://dx.doi.org/10.2147/JIR.S369690 |
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author | Nie, Qian-Qian Zheng, Zong-Qing Liao, Juan Li, Yu-Chao Chen, Yan-Ting Wang, Tian-Ye Yuan, Gui-Qiang Wang, Zhong Xue, Qun |
author_facet | Nie, Qian-Qian Zheng, Zong-Qing Liao, Juan Li, Yu-Chao Chen, Yan-Ting Wang, Tian-Ye Yuan, Gui-Qiang Wang, Zhong Xue, Qun |
author_sort | Nie, Qian-Qian |
collection | PubMed |
description | BACKGROUND: Ischemic injury in stroke is followed by extensive neurovascular inflammation and changes in ischemic penumbra gene expression patterns. However, the key molecules involved in the inflammatory response during the acute phase of ischemic stroke remain unclear. METHODS: Gene expression profiles of two rat ischemic stroke-related data sets, GSE61616 and GSE97537, were downloaded from the GEO database for Gene Set Enrichment Analysis (GSEA). Then, GEO2R was used to screen differentially expressed genes (DEGs). Furthermore, 170 differentially expressed intersection genes were screened and analyzed for Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Candidate genes and miRNAs were obtained by DAVID, Metascape, Cytoscape, STRING, and TargetScan. Finally, the rat middle cerebral artery occlusion-reperfusion (MCAO/R) model was constructed, and qRT-PCR was used to verify the predicted potential miRNA molecule and its target genes. RESULTS: GO and KEGG analyses showed that 170 genes were highly associated with inflammatory cell activation and cytokine production. After cluster analysis, seven hub genes highly correlated with post-stroke neuroinflammation were obtained: Cxcl1, Kng1, Il6, AnxA1, TIMP1, SPP1, and Ccl6. The results of TargetScan further suggested that miR-340-5p may negatively regulate SPP1, AnxA1, and TIMP1 simultaneously. In the ischemic penumbra of rats 24 h after MCAO/R, the level of miR-340-5p significantly decreased compared with the control group, while the concentration of SPP1, AnxA1, and TIMP1 increased. Time-course studies demonstrated that the mRNA expression levels of SPP1, AnxA1, and TIMP1 fluctuated dramatically throughout the acute phase of cerebral ischemia-reperfusion (I/R). CONCLUSION: Our study suggests that differentially expressed genes SPP1, TIMP1, and ANXA1 may play a vital role in the inflammatory response during the acute phase of cerebral ischemia-reperfusion injury. These genes may be negatively regulated by miR-340-5p. Our results may provide new insights into the complex pathophysiological mechanisms of secondary inflammation after stroke. |
format | Online Article Text |
id | pubmed-9420928 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-94209282022-08-30 SPP1/AnxA1/TIMP1 as Essential Genes Regulate the Inflammatory Response in the Acute Phase of Cerebral Ischemia-Reperfusion in Rats Nie, Qian-Qian Zheng, Zong-Qing Liao, Juan Li, Yu-Chao Chen, Yan-Ting Wang, Tian-Ye Yuan, Gui-Qiang Wang, Zhong Xue, Qun J Inflamm Res Original Research BACKGROUND: Ischemic injury in stroke is followed by extensive neurovascular inflammation and changes in ischemic penumbra gene expression patterns. However, the key molecules involved in the inflammatory response during the acute phase of ischemic stroke remain unclear. METHODS: Gene expression profiles of two rat ischemic stroke-related data sets, GSE61616 and GSE97537, were downloaded from the GEO database for Gene Set Enrichment Analysis (GSEA). Then, GEO2R was used to screen differentially expressed genes (DEGs). Furthermore, 170 differentially expressed intersection genes were screened and analyzed for Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Candidate genes and miRNAs were obtained by DAVID, Metascape, Cytoscape, STRING, and TargetScan. Finally, the rat middle cerebral artery occlusion-reperfusion (MCAO/R) model was constructed, and qRT-PCR was used to verify the predicted potential miRNA molecule and its target genes. RESULTS: GO and KEGG analyses showed that 170 genes were highly associated with inflammatory cell activation and cytokine production. After cluster analysis, seven hub genes highly correlated with post-stroke neuroinflammation were obtained: Cxcl1, Kng1, Il6, AnxA1, TIMP1, SPP1, and Ccl6. The results of TargetScan further suggested that miR-340-5p may negatively regulate SPP1, AnxA1, and TIMP1 simultaneously. In the ischemic penumbra of rats 24 h after MCAO/R, the level of miR-340-5p significantly decreased compared with the control group, while the concentration of SPP1, AnxA1, and TIMP1 increased. Time-course studies demonstrated that the mRNA expression levels of SPP1, AnxA1, and TIMP1 fluctuated dramatically throughout the acute phase of cerebral ischemia-reperfusion (I/R). CONCLUSION: Our study suggests that differentially expressed genes SPP1, TIMP1, and ANXA1 may play a vital role in the inflammatory response during the acute phase of cerebral ischemia-reperfusion injury. These genes may be negatively regulated by miR-340-5p. Our results may provide new insights into the complex pathophysiological mechanisms of secondary inflammation after stroke. Dove 2022-08-24 /pmc/articles/PMC9420928/ /pubmed/36046663 http://dx.doi.org/10.2147/JIR.S369690 Text en © 2022 Nie et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Nie, Qian-Qian Zheng, Zong-Qing Liao, Juan Li, Yu-Chao Chen, Yan-Ting Wang, Tian-Ye Yuan, Gui-Qiang Wang, Zhong Xue, Qun SPP1/AnxA1/TIMP1 as Essential Genes Regulate the Inflammatory Response in the Acute Phase of Cerebral Ischemia-Reperfusion in Rats |
title | SPP1/AnxA1/TIMP1 as Essential Genes Regulate the Inflammatory Response in the Acute Phase of Cerebral Ischemia-Reperfusion in Rats |
title_full | SPP1/AnxA1/TIMP1 as Essential Genes Regulate the Inflammatory Response in the Acute Phase of Cerebral Ischemia-Reperfusion in Rats |
title_fullStr | SPP1/AnxA1/TIMP1 as Essential Genes Regulate the Inflammatory Response in the Acute Phase of Cerebral Ischemia-Reperfusion in Rats |
title_full_unstemmed | SPP1/AnxA1/TIMP1 as Essential Genes Regulate the Inflammatory Response in the Acute Phase of Cerebral Ischemia-Reperfusion in Rats |
title_short | SPP1/AnxA1/TIMP1 as Essential Genes Regulate the Inflammatory Response in the Acute Phase of Cerebral Ischemia-Reperfusion in Rats |
title_sort | spp1/anxa1/timp1 as essential genes regulate the inflammatory response in the acute phase of cerebral ischemia-reperfusion in rats |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9420928/ https://www.ncbi.nlm.nih.gov/pubmed/36046663 http://dx.doi.org/10.2147/JIR.S369690 |
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