Analyzing gene expression profiles with preliminary validations in cardiac hypertrophy induced by pressure overload
Publication: Canadian Journal of Physiology and Pharmacology
6 March 2018
Abstract
The aim of this study was to identify the key genes involved in the cardiac hypertrophy (CH) induced by pressure overload. mRNA microarray data sets GSE5500 and GSE18801 were downloaded from the Gene Expression Omnibus database, and differentially expressed genes (DEGs) were screened using the Limma package; then, functional and pathway enrichment analysis were performed for common DEGs using the Database for Annotation, Visualization and Integrated Discovery database. Furthermore, the top DEGs were further validated using quantitative PCR in the hypertrophic heart tissue induced by isoprenaline. A total of 113 common DEGs with absolute fold change > 0.5, including 60 significantly upregulated DEGs and 53 downregulated DEGs, were obtained. Gene ontology term enrichment analysis suggested that common upregulated DEG were mainly enriched in neutrophil chemotaxis, extracellular fibril organization, and cell proliferation; and the common downregulated genes were significantly enriched in ion transport, endoplasmic reticulum, and dendritic spine. Kyoto Encyclopedia of Genes and Genomes pathway analysis found that the common DEGs were mainly enriched in extracellular matrix receptor interaction, phagosome, and focal adhesion. Additionally, the expression of Mfap4, Ltbp2, Aspn, Serpina3n, and Cnksr1 were upregulated in the model of CH, while the expression of Anp32a was downregulated. The current study identified the key deregulated genes and pathways involved in the CH, which could shed new light to understand the mechanism of CH.
Résumé
Cette étude avait pour but d’établir les gènes clés jouant un rôle dans l’hypertrophie cardiaque (HC) engendrée par une surcharge de pression. Nous avons téléversé les ensembles de données de biopuces d’ARNm GSE5500 et GSE18801 de la base de données GEO (pour « Gene Expression Omnibus »), et nous avons criblé des gènes exprimés de manière différentielle (GED) au moyen du progiciel Limma; puis, nous avons effectué une analyse d’enrichissement fonctionnel et des voies de signalisation pour les GED proéminents à l’aide de la base de données DAVID (pour « Database for Annotation, Visualisation and Integrated Discovery »). De plus, nous avons validé encore davantage les GED proéminents à l’aide de la technique de PCR quantitatif dans le tissu cardiaque hypertrophié engendré par l’isoprénaline. Nous avons obtenu au total 113 GED proéminents avec un double changement absolu inférieur à 0,5, y compris 60 GED nettement régulés à la hausse et 53 GED régulés à la baisse. L’analyse d’enrichissement des termes d’ontologie génique a laissé entrevoir que les GED proéminents régulés à la hausse s’enrichissaient principalement avec le chimiotactisme des neutrophiles, l’organisation des fibrilles extracellulaires et la prolifération cellulaire, tandis que les gènes proéminents régulés à la baisse s’enrichissaient de façon marquée avec le transport ionique, le réticulum endoplasmique et les épines dendritiques. L’analyse de la voie de signalisation KEGG (pour « Kyoto Encyclopedia of Genes and Genomes ») a montré que les GED proéminents s’enrichissaient principalement avec l’interaction du récepteur de la matrice extracellulaire, le phagosome et l’adhésion focale. De plus, l’expression des gènes Mfap4, Ltbp2, Aspn, Serpina3n et Cnksr1 était régulée à la hausse dans le modèle d’HC, tandis que l’expression du gène Anp32a était régulée à la baisse. La présente étude a permis d’établir les gènes et les voies de signalisation dérégulés jouant un rôle proéminent dans l’HC, ce qui pourrait jeter un nouvel éclairage permettant de comprendre les modes d’action inhérents à l’HC. [Traduit par la Rédaction]
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Published In
Canadian Journal of Physiology and Pharmacology
Volume 96 • Number 8 • August 2018
Pages: 701 - 709
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Received: 12 September 2017
Accepted: 15 December 2017
Accepted manuscript online: 6 March 2018
Version of record online: 6 March 2018
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Jing Gao, Yuhong Li, Tongmei Wang, Zhuo Shi, Yiqi Zhang, Shuang Liu, Pushuai Wen, and Chunyan Ma. 2018. Analyzing gene expression profiles with preliminary validations in cardiac hypertrophy induced by pressure overload. Canadian Journal of Physiology and Pharmacology. 96(8): 701-709. https://doi.org/10.1139/cjpp-2017-0585