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Comparative Transcriptional Analysis of Pulmonary Arterial Hypertension Associated With Three Different Diseases
Pulmonary arterial hypertension (PAH) is a severe cardiovascular disorder with high mortality. Multiple clinical diseases can induce PAH, but the underlying molecular mechanisms shared in PAHs associated with different diseases remain unclear. The aim of this study is to explore the key candidate ge...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319719/ https://www.ncbi.nlm.nih.gov/pubmed/34336829 http://dx.doi.org/10.3389/fcell.2021.672159 |
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author | Wang, Wei Jiang, Zhenhong Zhang, Dandan Fu, Linghua Wan, Rong Hong, Kui |
author_facet | Wang, Wei Jiang, Zhenhong Zhang, Dandan Fu, Linghua Wan, Rong Hong, Kui |
author_sort | Wang, Wei |
collection | PubMed |
description | Pulmonary arterial hypertension (PAH) is a severe cardiovascular disorder with high mortality. Multiple clinical diseases can induce PAH, but the underlying molecular mechanisms shared in PAHs associated with different diseases remain unclear. The aim of this study is to explore the key candidate genes and pathways in PAH associated with congenital heart disease (CHD-PAH), PAH associated with connective tissue disease (CTD-PAH), and idiopathic PAH (IPAH). We performed differential expression analysis based on a public microarray dataset GSE113439 and identified 1,442 differentially expressed genes, of which 80.3% were upregulated. Subsequently, both pathway enrichment analysis and protein–protein interaction network analysis revealed that the “Cell cycle” and “DNA damage” processes were significantly enriched in PAH. The expression of seven upregulated candidate genes (EIF2AK2, TOPBP1, CDC5L, DHX15, and CUL1–3) and three downregulated candidate genes (DLL4, EGFL7, and ACE) were validated by qRT-PCR. Furthermore, cell cycle-related genes Cul1 and Cul2 were identified in pulmonary arterial endothelial cells (PAECs) in vitro. The result revealed an increased expression of Cul2 in PAECs after hypoxic treatment. Silencing Cul2 could inhibit overproliferation and migration of PAECs in hypoxia. Taken together, according to bioinformatic analyses, our work revealed that “Cell cycle” and “DNA damage” process-related genes and pathways were significantly dysregulated expressed in PAHs associated with three different diseases. This commonality in molecular discovery might broaden the genetic perspective and understanding of PAH. Besides, silencing Cul2 showed a protective effect in PAECs in hypoxia. The results may provide new treatment targets in multiple diseases induced by PAH. |
format | Online Article Text |
id | pubmed-8319719 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83197192021-07-30 Comparative Transcriptional Analysis of Pulmonary Arterial Hypertension Associated With Three Different Diseases Wang, Wei Jiang, Zhenhong Zhang, Dandan Fu, Linghua Wan, Rong Hong, Kui Front Cell Dev Biol Cell and Developmental Biology Pulmonary arterial hypertension (PAH) is a severe cardiovascular disorder with high mortality. Multiple clinical diseases can induce PAH, but the underlying molecular mechanisms shared in PAHs associated with different diseases remain unclear. The aim of this study is to explore the key candidate genes and pathways in PAH associated with congenital heart disease (CHD-PAH), PAH associated with connective tissue disease (CTD-PAH), and idiopathic PAH (IPAH). We performed differential expression analysis based on a public microarray dataset GSE113439 and identified 1,442 differentially expressed genes, of which 80.3% were upregulated. Subsequently, both pathway enrichment analysis and protein–protein interaction network analysis revealed that the “Cell cycle” and “DNA damage” processes were significantly enriched in PAH. The expression of seven upregulated candidate genes (EIF2AK2, TOPBP1, CDC5L, DHX15, and CUL1–3) and three downregulated candidate genes (DLL4, EGFL7, and ACE) were validated by qRT-PCR. Furthermore, cell cycle-related genes Cul1 and Cul2 were identified in pulmonary arterial endothelial cells (PAECs) in vitro. The result revealed an increased expression of Cul2 in PAECs after hypoxic treatment. Silencing Cul2 could inhibit overproliferation and migration of PAECs in hypoxia. Taken together, according to bioinformatic analyses, our work revealed that “Cell cycle” and “DNA damage” process-related genes and pathways were significantly dysregulated expressed in PAHs associated with three different diseases. This commonality in molecular discovery might broaden the genetic perspective and understanding of PAH. Besides, silencing Cul2 showed a protective effect in PAECs in hypoxia. The results may provide new treatment targets in multiple diseases induced by PAH. Frontiers Media S.A. 2021-07-15 /pmc/articles/PMC8319719/ /pubmed/34336829 http://dx.doi.org/10.3389/fcell.2021.672159 Text en Copyright © 2021 Wang, Jiang, Zhang, Fu, Wan and Hong. https://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 | Cell and Developmental Biology Wang, Wei Jiang, Zhenhong Zhang, Dandan Fu, Linghua Wan, Rong Hong, Kui Comparative Transcriptional Analysis of Pulmonary Arterial Hypertension Associated With Three Different Diseases |
title | Comparative Transcriptional Analysis of Pulmonary Arterial Hypertension Associated With Three Different Diseases |
title_full | Comparative Transcriptional Analysis of Pulmonary Arterial Hypertension Associated With Three Different Diseases |
title_fullStr | Comparative Transcriptional Analysis of Pulmonary Arterial Hypertension Associated With Three Different Diseases |
title_full_unstemmed | Comparative Transcriptional Analysis of Pulmonary Arterial Hypertension Associated With Three Different Diseases |
title_short | Comparative Transcriptional Analysis of Pulmonary Arterial Hypertension Associated With Three Different Diseases |
title_sort | comparative transcriptional analysis of pulmonary arterial hypertension associated with three different diseases |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319719/ https://www.ncbi.nlm.nih.gov/pubmed/34336829 http://dx.doi.org/10.3389/fcell.2021.672159 |
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