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...
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.672159/full |
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| author | Wei Wang Zhenhong Jiang Zhenhong Jiang Dandan Zhang Linghua Fu Rong Wan Kui Hong Kui Hong |
| author_facet | Wei Wang Zhenhong Jiang Zhenhong Jiang Dandan Zhang Linghua Fu Rong Wan Kui Hong Kui Hong |
| author_sort | Wei Wang |
| collection | DOAJ |
| 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. |
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| language | English |
| last_indexed | 2024-12-17T03:00:52Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-1f6a13328b984c1cae3e67212c5464d62022-12-21T22:06:05ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-07-01910.3389/fcell.2021.672159672159Comparative Transcriptional Analysis of Pulmonary Arterial Hypertension Associated With Three Different DiseasesWei Wang0Zhenhong Jiang1Zhenhong Jiang2Dandan Zhang3Linghua Fu4Rong Wan5Kui Hong6Kui Hong7Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaJiangxi Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaJiangxi Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaJiangxi Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaPulmonary 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.https://www.frontiersin.org/articles/10.3389/fcell.2021.672159/fullpulmonary arterial hypertensiongene and pathway enrichment analysesprotein-protein interactioncell cycleDNA damageCUL2 |
| spellingShingle | Wei Wang Zhenhong Jiang Zhenhong Jiang Dandan Zhang Linghua Fu Rong Wan Kui Hong Kui Hong Comparative Transcriptional Analysis of Pulmonary Arterial Hypertension Associated With Three Different Diseases Frontiers in Cell and Developmental Biology pulmonary arterial hypertension gene and pathway enrichment analyses protein-protein interaction cell cycle DNA damage CUL2 |
| 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 | pulmonary arterial hypertension gene and pathway enrichment analyses protein-protein interaction cell cycle DNA damage CUL2 |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.672159/full |
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