Identification of Hypoxia Induced Metabolism Associated Genes in Pulmonary Hypertension

Objective: Pulmonary hypertension (PH) associated with hypoxia and lung disease (Group 3) is the second most common form of PH and associated with increased morbidity and mortality. This study was aimed to identify hypoxia induced metabolism associated genes (MAGs) for better understanding of hypoxi...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yang-Yang He, Xin-Mei Xie, Hong-Da Zhang, Jue Ye, Selin Gencer, Emiel P. C. van der Vorst, Yvonne Döring, Christian Weber, Xiao-Bin Pang, Zhi-Cheng Jing, Yi Yan, Zhi-Yan Han
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	pulmonary hypertension hypoxia metabolism associated genes metabolomics transcriptomics Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/78cc3f708b484c899b8b969a331d8b4b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:78cc3f708b484c899b8b969a331d8b4b
record_format	dspace
spelling	oai:doaj.org-article:78cc3f708b484c899b8b969a331d8b4b2021-11-05T11:39:48ZIdentification of Hypoxia Induced Metabolism Associated Genes in Pulmonary Hypertension1663-981210.3389/fphar.2021.753727https://doaj.org/article/78cc3f708b484c899b8b969a331d8b4b2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.753727/fullhttps://doaj.org/toc/1663-9812Objective: Pulmonary hypertension (PH) associated with hypoxia and lung disease (Group 3) is the second most common form of PH and associated with increased morbidity and mortality. This study was aimed to identify hypoxia induced metabolism associated genes (MAGs) for better understanding of hypoxic PH.Methods: Rat pulmonary arterial smooth muscle cells (PASMCs) were isolated and cultured in normoxic or hypoxic condition for 24 h. Cells were harvested for liquid chromatography-mass spectrometry analysis. Functional annotation of distinguishing metabolites was performed using Metaboanalyst. Top 10 enriched metabolite sets were selected for the identification of metabolism associated genes (MAGs) with a relevance score >8 in Genecards. Transcriptomic data from lungs of hypoxic PH in mice/rats or of PH patients were accessed from Gene Expression Omnibus (GEO) database or open-access online platform. Connectivity Map analysis was performed to identify potential compounds to reverse the metabolism associated gene profile under hypoxia stress. The construction and module analysis of the protein-protein interaction (PPI) network was performed. Hub genes were then identified and used to generate LASSO model to determine its accuracy to predict occurrence of PH.Results: A total of 36 altered metabolites and 1,259 unique MAGs were identified in rat PASMCs under hypoxia. 38 differentially expressed MAGs in mouse lungs of hypoxic PH were revealed, with enrichment in multi-pathways including regulation of glucose metabolic process, which might be reversed by drugs such as blebbistatin. 5 differentially expressed MAGs were displayed in SMCs of Sugen 5416/hypoxia induced PH rats at the single cell resolution. Furthermore, 6 hub genes (Cat, Ephx1, Gpx3, Gstm4, Gstm5, and Gsto1) out of 42 unique hypoxia induced MAGs were identified. Higher Cat, Ephx1 and lower Gsto1 were displayed in mouse lungs under hypoxia (all p < 0.05), in consistent with the alteration in lungs of PH patients. The hub gene-based LASSO model can predict the occurrence of PH (AUC = 0.90).Conclusion: Our findings revealed six hypoxia-induced metabolism associated hub genes, and shed some light on the molecular mechanism and therapeutic targets in hypoxic PH.Yang-Yang HeXin-Mei XieHong-Da ZhangJue YeSelin GencerEmiel P. C. van der VorstEmiel P. C. van der VorstEmiel P. C. van der VorstEmiel P. C. van der VorstEmiel P. C. van der VorstYvonne DöringYvonne DöringYvonne DöringChristian WeberChristian WeberChristian WeberChristian WeberXiao-Bin PangZhi-Cheng JingYi YanYi YanZhi-Yan HanFrontiers Media S.A.articlepulmonary hypertensionhypoxiametabolism associated genesmetabolomicstranscriptomicsTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	pulmonary hypertension hypoxia metabolism associated genes metabolomics transcriptomics Therapeutics. Pharmacology RM1-950
spellingShingle	pulmonary hypertension hypoxia metabolism associated genes metabolomics transcriptomics Therapeutics. Pharmacology RM1-950 Yang-Yang He Xin-Mei Xie Hong-Da Zhang Jue Ye Selin Gencer Emiel P. C. van der Vorst Emiel P. C. van der Vorst Emiel P. C. van der Vorst Emiel P. C. van der Vorst Emiel P. C. van der Vorst Yvonne Döring Yvonne Döring Yvonne Döring Christian Weber Christian Weber Christian Weber Christian Weber Xiao-Bin Pang Zhi-Cheng Jing Yi Yan Yi Yan Zhi-Yan Han Identification of Hypoxia Induced Metabolism Associated Genes in Pulmonary Hypertension
description	Objective: Pulmonary hypertension (PH) associated with hypoxia and lung disease (Group 3) is the second most common form of PH and associated with increased morbidity and mortality. This study was aimed to identify hypoxia induced metabolism associated genes (MAGs) for better understanding of hypoxic PH.Methods: Rat pulmonary arterial smooth muscle cells (PASMCs) were isolated and cultured in normoxic or hypoxic condition for 24 h. Cells were harvested for liquid chromatography-mass spectrometry analysis. Functional annotation of distinguishing metabolites was performed using Metaboanalyst. Top 10 enriched metabolite sets were selected for the identification of metabolism associated genes (MAGs) with a relevance score >8 in Genecards. Transcriptomic data from lungs of hypoxic PH in mice/rats or of PH patients were accessed from Gene Expression Omnibus (GEO) database or open-access online platform. Connectivity Map analysis was performed to identify potential compounds to reverse the metabolism associated gene profile under hypoxia stress. The construction and module analysis of the protein-protein interaction (PPI) network was performed. Hub genes were then identified and used to generate LASSO model to determine its accuracy to predict occurrence of PH.Results: A total of 36 altered metabolites and 1,259 unique MAGs were identified in rat PASMCs under hypoxia. 38 differentially expressed MAGs in mouse lungs of hypoxic PH were revealed, with enrichment in multi-pathways including regulation of glucose metabolic process, which might be reversed by drugs such as blebbistatin. 5 differentially expressed MAGs were displayed in SMCs of Sugen 5416/hypoxia induced PH rats at the single cell resolution. Furthermore, 6 hub genes (Cat, Ephx1, Gpx3, Gstm4, Gstm5, and Gsto1) out of 42 unique hypoxia induced MAGs were identified. Higher Cat, Ephx1 and lower Gsto1 were displayed in mouse lungs under hypoxia (all p < 0.05), in consistent with the alteration in lungs of PH patients. The hub gene-based LASSO model can predict the occurrence of PH (AUC = 0.90).Conclusion: Our findings revealed six hypoxia-induced metabolism associated hub genes, and shed some light on the molecular mechanism and therapeutic targets in hypoxic PH.
format	article
author	Yang-Yang He Xin-Mei Xie Hong-Da Zhang Jue Ye Selin Gencer Emiel P. C. van der Vorst Emiel P. C. van der Vorst Emiel P. C. van der Vorst Emiel P. C. van der Vorst Emiel P. C. van der Vorst Yvonne Döring Yvonne Döring Yvonne Döring Christian Weber Christian Weber Christian Weber Christian Weber Xiao-Bin Pang Zhi-Cheng Jing Yi Yan Yi Yan Zhi-Yan Han
author_facet	Yang-Yang He Xin-Mei Xie Hong-Da Zhang Jue Ye Selin Gencer Emiel P. C. van der Vorst Emiel P. C. van der Vorst Emiel P. C. van der Vorst Emiel P. C. van der Vorst Emiel P. C. van der Vorst Yvonne Döring Yvonne Döring Yvonne Döring Christian Weber Christian Weber Christian Weber Christian Weber Xiao-Bin Pang Zhi-Cheng Jing Yi Yan Yi Yan Zhi-Yan Han
author_sort	Yang-Yang He
title	Identification of Hypoxia Induced Metabolism Associated Genes in Pulmonary Hypertension
title_short	Identification of Hypoxia Induced Metabolism Associated Genes in Pulmonary Hypertension
title_full	Identification of Hypoxia Induced Metabolism Associated Genes in Pulmonary Hypertension
title_fullStr	Identification of Hypoxia Induced Metabolism Associated Genes in Pulmonary Hypertension
title_full_unstemmed	Identification of Hypoxia Induced Metabolism Associated Genes in Pulmonary Hypertension
title_sort	identification of hypoxia induced metabolism associated genes in pulmonary hypertension
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/78cc3f708b484c899b8b969a331d8b4b
work_keys_str_mv	AT yangyanghe identificationofhypoxiainducedmetabolismassociatedgenesinpulmonaryhypertension AT xinmeixie identificationofhypoxiainducedmetabolismassociatedgenesinpulmonaryhypertension AT hongdazhang identificationofhypoxiainducedmetabolismassociatedgenesinpulmonaryhypertension AT jueye identificationofhypoxiainducedmetabolismassociatedgenesinpulmonaryhypertension AT selingencer identificationofhypoxiainducedmetabolismassociatedgenesinpulmonaryhypertension AT emielpcvandervorst identificationofhypoxiainducedmetabolismassociatedgenesinpulmonaryhypertension AT emielpcvandervorst identificationofhypoxiainducedmetabolismassociatedgenesinpulmonaryhypertension AT emielpcvandervorst identificationofhypoxiainducedmetabolismassociatedgenesinpulmonaryhypertension AT emielpcvandervorst identificationofhypoxiainducedmetabolismassociatedgenesinpulmonaryhypertension AT emielpcvandervorst identificationofhypoxiainducedmetabolismassociatedgenesinpulmonaryhypertension AT yvonnedoring identificationofhypoxiainducedmetabolismassociatedgenesinpulmonaryhypertension AT yvonnedoring identificationofhypoxiainducedmetabolismassociatedgenesinpulmonaryhypertension AT yvonnedoring identificationofhypoxiainducedmetabolismassociatedgenesinpulmonaryhypertension AT christianweber identificationofhypoxiainducedmetabolismassociatedgenesinpulmonaryhypertension AT christianweber identificationofhypoxiainducedmetabolismassociatedgenesinpulmonaryhypertension AT christianweber identificationofhypoxiainducedmetabolismassociatedgenesinpulmonaryhypertension AT christianweber identificationofhypoxiainducedmetabolismassociatedgenesinpulmonaryhypertension AT xiaobinpang identificationofhypoxiainducedmetabolismassociatedgenesinpulmonaryhypertension AT zhichengjing identificationofhypoxiainducedmetabolismassociatedgenesinpulmonaryhypertension AT yiyan identificationofhypoxiainducedmetabolismassociatedgenesinpulmonaryhypertension AT yiyan identificationofhypoxiainducedmetabolismassociatedgenesinpulmonaryhypertension AT zhiyanhan identificationofhypoxiainducedmetabolismassociatedgenesinpulmonaryhypertension
_version_	1718444297309650944

Identification of Hypoxia Induced Metabolism Associated Genes in Pulmonary Hypertension

Ejemplares similares