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Critical Roles of ELVOL4 and IL-33 in the Progression of Obesity-Related Cardiomyopathy via Integrated Bioinformatics Analysis

The molecular mechanisms underlying obesity-related cardiomyopathy (ORCM) progression involve multiple signaling pathways, and the pharmacological treatment for ORCM is still limited. Thus, it is necessary to explore new targets and develop novel therapies. Microarray analysis for gene expression pr...

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Autores principales: Tao, Jun, Wang, Yajing, Li, Ling, Zheng, Junmeng, Liang, Shi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291781/
https://www.ncbi.nlm.nih.gov/pubmed/32581837
http://dx.doi.org/10.3389/fphys.2020.00542
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author Tao, Jun
Wang, Yajing
Li, Ling
Zheng, Junmeng
Liang, Shi
author_facet Tao, Jun
Wang, Yajing
Li, Ling
Zheng, Junmeng
Liang, Shi
author_sort Tao, Jun
collection PubMed
description The molecular mechanisms underlying obesity-related cardiomyopathy (ORCM) progression involve multiple signaling pathways, and the pharmacological treatment for ORCM is still limited. Thus, it is necessary to explore new targets and develop novel therapies. Microarray analysis for gene expression profiles using different bioinformatics tools has been an effective strategy for identifying novel targets for various diseases. In this study, we aimed to explore the potential genes related to ORCM using the integrated bioinformatics analysis. The GSE18897 (whole blood expression profiling of obese diet-sensitive, obese diet-resistant, and lean human subjects) and GSE47022 (regular weight C57BL/6 and diet-induced obese C57BL/6 mice) were used for bioinformatics analysis. Weighted gene co-expression network analysis (WGCNA) of GSE18897 was employed to investigate gene modules that were strongly correlated with clinical phenotypes. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the co-expression genes. The expression levels of the hub genes were validated in the clinical samples. Yellow co-expression module of WGCNA in GSE18897 was found to be significantly related to the caloric restriction treatment. In addition, GO functional enrichment analysis and KEGG pathway analysis were performed on the co-expression genes in yellow co-expression module, which showed an association with oxygen transport and the porphyrins pathway. Overlap analysis of yellow co-expression module genes from GSE18897 andGSE47022 revealed six upregulated genes, and further experimental validation results showed that elongation of very-long-chain fatty acids protein 4 (ELOVL4), matrix metalloproteinase-8 (MMP-8), and interleukin-33 (IL-33) were upregulated in the peripheral blood from patients with ORCM compared to that in the controls. The bioinformatics analysis revealed that ELOVL4 expression levels are positively correlated with that of IL-33. Collectively, using WGCNA in combination with integrated bioinformatics analysis, the hub genes of ELVOL4 and IL-33 might serve as potential biomarkers for diagnosis and/or therapeutic targets for ORCM. The detailed roles of ELVOL4 and IL-33 in the pathophysiology of ORCM still require further investigation.
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spelling pubmed-72917812020-06-23 Critical Roles of ELVOL4 and IL-33 in the Progression of Obesity-Related Cardiomyopathy via Integrated Bioinformatics Analysis Tao, Jun Wang, Yajing Li, Ling Zheng, Junmeng Liang, Shi Front Physiol Physiology The molecular mechanisms underlying obesity-related cardiomyopathy (ORCM) progression involve multiple signaling pathways, and the pharmacological treatment for ORCM is still limited. Thus, it is necessary to explore new targets and develop novel therapies. Microarray analysis for gene expression profiles using different bioinformatics tools has been an effective strategy for identifying novel targets for various diseases. In this study, we aimed to explore the potential genes related to ORCM using the integrated bioinformatics analysis. The GSE18897 (whole blood expression profiling of obese diet-sensitive, obese diet-resistant, and lean human subjects) and GSE47022 (regular weight C57BL/6 and diet-induced obese C57BL/6 mice) were used for bioinformatics analysis. Weighted gene co-expression network analysis (WGCNA) of GSE18897 was employed to investigate gene modules that were strongly correlated with clinical phenotypes. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the co-expression genes. The expression levels of the hub genes were validated in the clinical samples. Yellow co-expression module of WGCNA in GSE18897 was found to be significantly related to the caloric restriction treatment. In addition, GO functional enrichment analysis and KEGG pathway analysis were performed on the co-expression genes in yellow co-expression module, which showed an association with oxygen transport and the porphyrins pathway. Overlap analysis of yellow co-expression module genes from GSE18897 andGSE47022 revealed six upregulated genes, and further experimental validation results showed that elongation of very-long-chain fatty acids protein 4 (ELOVL4), matrix metalloproteinase-8 (MMP-8), and interleukin-33 (IL-33) were upregulated in the peripheral blood from patients with ORCM compared to that in the controls. The bioinformatics analysis revealed that ELOVL4 expression levels are positively correlated with that of IL-33. Collectively, using WGCNA in combination with integrated bioinformatics analysis, the hub genes of ELVOL4 and IL-33 might serve as potential biomarkers for diagnosis and/or therapeutic targets for ORCM. The detailed roles of ELVOL4 and IL-33 in the pathophysiology of ORCM still require further investigation. Frontiers Media S.A. 2020-06-05 /pmc/articles/PMC7291781/ /pubmed/32581837 http://dx.doi.org/10.3389/fphys.2020.00542 Text en Copyright © 2020 Tao, Wang, Li, Zheng and Liang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Tao, Jun
Wang, Yajing
Li, Ling
Zheng, Junmeng
Liang, Shi
Critical Roles of ELVOL4 and IL-33 in the Progression of Obesity-Related Cardiomyopathy via Integrated Bioinformatics Analysis
title Critical Roles of ELVOL4 and IL-33 in the Progression of Obesity-Related Cardiomyopathy via Integrated Bioinformatics Analysis
title_full Critical Roles of ELVOL4 and IL-33 in the Progression of Obesity-Related Cardiomyopathy via Integrated Bioinformatics Analysis
title_fullStr Critical Roles of ELVOL4 and IL-33 in the Progression of Obesity-Related Cardiomyopathy via Integrated Bioinformatics Analysis
title_full_unstemmed Critical Roles of ELVOL4 and IL-33 in the Progression of Obesity-Related Cardiomyopathy via Integrated Bioinformatics Analysis
title_short Critical Roles of ELVOL4 and IL-33 in the Progression of Obesity-Related Cardiomyopathy via Integrated Bioinformatics Analysis
title_sort critical roles of elvol4 and il-33 in the progression of obesity-related cardiomyopathy via integrated bioinformatics analysis
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291781/
https://www.ncbi.nlm.nih.gov/pubmed/32581837
http://dx.doi.org/10.3389/fphys.2020.00542
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