Identification of TLR2 as a Key Target in Neuroinflammation in Vascular Dementia

Vascular dementia (VaD) is the second most common cause of dementia. At present, precise molecular processes of VaD are unclear. We attempted to discover the VaD relevant candidate genes, enrichment biological processes and pathways, key targets, and the underlying mechanism by microarray bioinforma...

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Main Authors: Yuye Wang, Shuang Lv, Xiao Zhou, Xiaoqian Niu, Leian Chen, Ziyuan Yang, Dantao Peng
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-07-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2022.860122/full
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author Yuye Wang
Yuye Wang
Shuang Lv
Shuang Lv
Xiao Zhou
Xiao Zhou
Xiaoqian Niu
Xiaoqian Niu
Leian Chen
Leian Chen
Ziyuan Yang
Ziyuan Yang
Dantao Peng
Dantao Peng
Dantao Peng
author_facet Yuye Wang
Yuye Wang
Shuang Lv
Shuang Lv
Xiao Zhou
Xiao Zhou
Xiaoqian Niu
Xiaoqian Niu
Leian Chen
Leian Chen
Ziyuan Yang
Ziyuan Yang
Dantao Peng
Dantao Peng
Dantao Peng
author_sort Yuye Wang
collection DOAJ
description Vascular dementia (VaD) is the second most common cause of dementia. At present, precise molecular processes of VaD are unclear. We attempted to discover the VaD relevant candidate genes, enrichment biological processes and pathways, key targets, and the underlying mechanism by microarray bioinformatic analysis. We selected GSE122063 related to the autopsy samples of VaD for analysis. We first took use of Weighted Gene Co-expression Network Analysis (WGCNA) to achieve modules related to VaD and hub genes. Second, we filtered out significant differentially expressed genes (DEGs). Third, significant DEGs then went through Geno Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Fourth, Gene Set Enrichment Analysis (GSEA) was performed. At last, we constructed the protein–protein interaction (PPI) network. The results showed that the yellow module had the strongest correlation with VaD, and we finally identified 21 hub genes. Toll-like receptor 2 (TLR2) was the top hub gene and was strongly correlated with other possible candidate genes. In total, 456 significant DEGs were filtered out and these genes were found to be enriched in the Toll receptor signaling pathway and several other immune-related pathways. In addition, Gene Set Enrichment Analysis results showed that similar pathways were significantly over-represented in TLR2-high samples. In the PPI network, TLR2 was still an important node with high weight and combined scores. We concluded that the TLR2 acts as a key target in neuroinflammation which may participate in the pathophysiological process of VaD.
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spelling doaj.art-1f569bfac931462b92a36b318c643cfc2022-12-22T02:26:42ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-07-011310.3389/fgene.2022.860122860122Identification of TLR2 as a Key Target in Neuroinflammation in Vascular DementiaYuye Wang0Yuye Wang1Shuang Lv2Shuang Lv3Xiao Zhou4Xiao Zhou5Xiaoqian Niu6Xiaoqian Niu7Leian Chen8Leian Chen9Ziyuan Yang10Ziyuan Yang11Dantao Peng12Dantao Peng13Dantao Peng14Department of Neurology, China-Japan Friendship Hospital, Beijing, ChinaGraduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Neurology, China-Japan Friendship Hospital, Beijing, ChinaPeking University China-Japan Friendship School of Clinical Medicine, Beijing, ChinaDepartment of Neurology, China-Japan Friendship Hospital, Beijing, ChinaGraduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Neurology, China-Japan Friendship Hospital, Beijing, ChinaPeking University China-Japan Friendship School of Clinical Medicine, Beijing, ChinaDepartment of Neurology, China-Japan Friendship Hospital, Beijing, ChinaGraduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Neurology, China-Japan Friendship Hospital, Beijing, ChinaPeking University China-Japan Friendship School of Clinical Medicine, Beijing, ChinaDepartment of Neurology, China-Japan Friendship Hospital, Beijing, ChinaGraduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, ChinaPeking University China-Japan Friendship School of Clinical Medicine, Beijing, ChinaVascular dementia (VaD) is the second most common cause of dementia. At present, precise molecular processes of VaD are unclear. We attempted to discover the VaD relevant candidate genes, enrichment biological processes and pathways, key targets, and the underlying mechanism by microarray bioinformatic analysis. We selected GSE122063 related to the autopsy samples of VaD for analysis. We first took use of Weighted Gene Co-expression Network Analysis (WGCNA) to achieve modules related to VaD and hub genes. Second, we filtered out significant differentially expressed genes (DEGs). Third, significant DEGs then went through Geno Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Fourth, Gene Set Enrichment Analysis (GSEA) was performed. At last, we constructed the protein–protein interaction (PPI) network. The results showed that the yellow module had the strongest correlation with VaD, and we finally identified 21 hub genes. Toll-like receptor 2 (TLR2) was the top hub gene and was strongly correlated with other possible candidate genes. In total, 456 significant DEGs were filtered out and these genes were found to be enriched in the Toll receptor signaling pathway and several other immune-related pathways. In addition, Gene Set Enrichment Analysis results showed that similar pathways were significantly over-represented in TLR2-high samples. In the PPI network, TLR2 was still an important node with high weight and combined scores. We concluded that the TLR2 acts as a key target in neuroinflammation which may participate in the pathophysiological process of VaD.https://www.frontiersin.org/articles/10.3389/fgene.2022.860122/fullvascular dementiaTLR2neuroinflammationbioinformatic analysisWGCNA
spellingShingle Yuye Wang
Yuye Wang
Shuang Lv
Shuang Lv
Xiao Zhou
Xiao Zhou
Xiaoqian Niu
Xiaoqian Niu
Leian Chen
Leian Chen
Ziyuan Yang
Ziyuan Yang
Dantao Peng
Dantao Peng
Dantao Peng
Identification of TLR2 as a Key Target in Neuroinflammation in Vascular Dementia
Frontiers in Genetics
vascular dementia
TLR2
neuroinflammation
bioinformatic analysis
WGCNA
title Identification of TLR2 as a Key Target in Neuroinflammation in Vascular Dementia
title_full Identification of TLR2 as a Key Target in Neuroinflammation in Vascular Dementia
title_fullStr Identification of TLR2 as a Key Target in Neuroinflammation in Vascular Dementia
title_full_unstemmed Identification of TLR2 as a Key Target in Neuroinflammation in Vascular Dementia
title_short Identification of TLR2 as a Key Target in Neuroinflammation in Vascular Dementia
title_sort identification of tlr2 as a key target in neuroinflammation in vascular dementia
topic vascular dementia
TLR2
neuroinflammation
bioinformatic analysis
WGCNA
url https://www.frontiersin.org/articles/10.3389/fgene.2022.860122/full
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