Upregulation of key genes Eln and Tgfb3 were associated with the severity of cardiac hypertrophy

Abstract Background Hypertension-induced cardiac hypertrophy is one of the most common pre-conditions that accompanies heart failure. This study aimed to identify the key pathogenic genes in the disease process. Methods GSE18224 was re-analyzed and differentially expressed genes (DEGs) were obtained...

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Main Authors: Rui Zhang, Xuan Xu, Xi Chen, Chunshu Hao, Zhenjun Ji, Pengfei Zuo, Mingming Yang, Genshan Ma, Yongjun Li
Format: Article
Language:English
Published: BMC 2022-08-01
Series:BMC Genomics
Subjects:
Online Access:https://doi.org/10.1186/s12864-022-08778-0
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author Rui Zhang
Xuan Xu
Xi Chen
Chunshu Hao
Zhenjun Ji
Pengfei Zuo
Mingming Yang
Genshan Ma
Yongjun Li
author_facet Rui Zhang
Xuan Xu
Xi Chen
Chunshu Hao
Zhenjun Ji
Pengfei Zuo
Mingming Yang
Genshan Ma
Yongjun Li
author_sort Rui Zhang
collection DOAJ
description Abstract Background Hypertension-induced cardiac hypertrophy is one of the most common pre-conditions that accompanies heart failure. This study aimed to identify the key pathogenic genes in the disease process. Methods GSE18224 was re-analyzed and differentially expressed genes (DEGs) were obtained. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out. Networks of transcription factor (TF)-mRNA, microRNA (miRNA)-mRNA and Protein-Protein interaction (PPI) were constructed, and a key module was further screened out from PPI network. GSE36074 dataset and our transverse aortic constriction (TAC) mouse model were used to validate gene expression in the module. Finally, the correlation between the genes and biomarkers of cardiac hypertrophy were evaluated. Results Totally, there were 348 DEGs in GSE18224, which were mainly enriched in biological processes including collagen fibril organization, cellular response to transforming growth factor-beta stimulus and were involved in ECM-receptor interaction and Oxytocin signaling pathway. There were 387 miRNAs targeted by 257 DEGs, while 177 TFs targeted 71 DEGs. The PPI network contained 222 nodes and 770 edges, with 18 genes screened out into the module. After validation, 8 genes, which were also significantly upregulated in the GSE36074 dataset, were selected from the 18 DEGs. 2 of the 8 DEGs, including Eln and Tgfb3 were significantly upregulated in our mouse model of myocardial hypertrophy. Finally, the expression of Eln and Tgfb3 were found to be positively correlated with the level of the disease biomarkers. Conclusions Upregulated key genes Eln and Tgfb3 were positively correlated with the severity of cardiac hypertrophy, which may provide potential therapeutic targets for the disease.
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spelling doaj.art-0c3c3983bbd3447d97867b28a2c46f5b2022-12-22T01:35:43ZengBMCBMC Genomics1471-21642022-08-0123111210.1186/s12864-022-08778-0Upregulation of key genes Eln and Tgfb3 were associated with the severity of cardiac hypertrophyRui Zhang0Xuan Xu1Xi Chen2Chunshu Hao3Zhenjun Ji4Pengfei Zuo5Mingming Yang6Genshan Ma7Yongjun Li8Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast UniversityDepartment of Cardiology, Zhongda Hospital, School of Medicine, Southeast UniversityDepartment of Cardiology, Zhongda Hospital, School of Medicine, Southeast UniversityDepartment of Cardiology, Zhongda Hospital, School of Medicine, Southeast UniversityDepartment of Cardiology, Zhongda Hospital, School of Medicine, Southeast UniversityDepartment of Cardiology, Zhongda Hospital, School of Medicine, Southeast UniversityDepartment of Cardiology, Zhongda Hospital, School of Medicine, Southeast UniversityDepartment of Cardiology, Zhongda Hospital, School of Medicine, Southeast UniversityDepartment of Cardiology, Zhongda Hospital, School of Medicine, Southeast UniversityAbstract Background Hypertension-induced cardiac hypertrophy is one of the most common pre-conditions that accompanies heart failure. This study aimed to identify the key pathogenic genes in the disease process. Methods GSE18224 was re-analyzed and differentially expressed genes (DEGs) were obtained. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out. Networks of transcription factor (TF)-mRNA, microRNA (miRNA)-mRNA and Protein-Protein interaction (PPI) were constructed, and a key module was further screened out from PPI network. GSE36074 dataset and our transverse aortic constriction (TAC) mouse model were used to validate gene expression in the module. Finally, the correlation between the genes and biomarkers of cardiac hypertrophy were evaluated. Results Totally, there were 348 DEGs in GSE18224, which were mainly enriched in biological processes including collagen fibril organization, cellular response to transforming growth factor-beta stimulus and were involved in ECM-receptor interaction and Oxytocin signaling pathway. There were 387 miRNAs targeted by 257 DEGs, while 177 TFs targeted 71 DEGs. The PPI network contained 222 nodes and 770 edges, with 18 genes screened out into the module. After validation, 8 genes, which were also significantly upregulated in the GSE36074 dataset, were selected from the 18 DEGs. 2 of the 8 DEGs, including Eln and Tgfb3 were significantly upregulated in our mouse model of myocardial hypertrophy. Finally, the expression of Eln and Tgfb3 were found to be positively correlated with the level of the disease biomarkers. Conclusions Upregulated key genes Eln and Tgfb3 were positively correlated with the severity of cardiac hypertrophy, which may provide potential therapeutic targets for the disease.https://doi.org/10.1186/s12864-022-08778-0Cardiac hypertrophyBioinformaticsGEO databaseKey gene
spellingShingle Rui Zhang
Xuan Xu
Xi Chen
Chunshu Hao
Zhenjun Ji
Pengfei Zuo
Mingming Yang
Genshan Ma
Yongjun Li
Upregulation of key genes Eln and Tgfb3 were associated with the severity of cardiac hypertrophy
BMC Genomics
Cardiac hypertrophy
Bioinformatics
GEO database
Key gene
title Upregulation of key genes Eln and Tgfb3 were associated with the severity of cardiac hypertrophy
title_full Upregulation of key genes Eln and Tgfb3 were associated with the severity of cardiac hypertrophy
title_fullStr Upregulation of key genes Eln and Tgfb3 were associated with the severity of cardiac hypertrophy
title_full_unstemmed Upregulation of key genes Eln and Tgfb3 were associated with the severity of cardiac hypertrophy
title_short Upregulation of key genes Eln and Tgfb3 were associated with the severity of cardiac hypertrophy
title_sort upregulation of key genes eln and tgfb3 were associated with the severity of cardiac hypertrophy
topic Cardiac hypertrophy
Bioinformatics
GEO database
Key gene
url https://doi.org/10.1186/s12864-022-08778-0
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