Ace2 and Tmprss2 Expressions Are Regulated by Dhx32 and Influence the Gastrointestinal Symptoms Caused by SARS-CoV-2

Studies showed that the gastrointestinal (GI) tract is one of the most important pathways for SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19). As SARS-CoV-2 cellular entry depends on the ACE2 receptor and TMPRSS2 priming of the spike protein, it is important to understand the molecular...

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Autores principales:	Fuyi Xu, Jun Gao, Buyan-Ochir Orgil, Akhilesh Kumar Bajpai, Qingqing Gu, Enkhsaikhan Purevjav, Athena S. Davenport, Kui Li, Jeffrey A. Towbin, Dennis D. Black, Joseph F. Pierre, Lu Lu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	BXD mice gastrointestinal tract transcriptome co-expression COVID-19 SARS-CoV-2 Medicine R
Acceso en línea:	https://doaj.org/article/c76ba44428a94ab795261a539ab9c493
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spelling	oai:doaj.org-article:c76ba44428a94ab795261a539ab9c4932021-11-25T18:08:03Z<i>Ace2</i> and <i>Tmprss2</i> Expressions Are Regulated by <i>Dhx32</i> and Influence the Gastrointestinal Symptoms Caused by SARS-CoV-210.3390/jpm111112122075-4426https://doaj.org/article/c76ba44428a94ab795261a539ab9c4932021-11-01T00:00:00Zhttps://www.mdpi.com/2075-4426/11/11/1212https://doaj.org/toc/2075-4426Studies showed that the gastrointestinal (GI) tract is one of the most important pathways for SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19). As SARS-CoV-2 cellular entry depends on the ACE2 receptor and TMPRSS2 priming of the spike protein, it is important to understand the molecular mechanisms through which these two proteins and their cognate transcripts interact and influence the pathogenesis of COVID-19. In this study, we quantified the expression, associations, genetic modulators, and molecular pathways for <i>Tmprss2</i> and <i>Ace2</i> mRNA expressions in GI tissues using a systems genetics approach and the expanded family of highly diverse BXD mouse strains. The results showed that both <i>Tmprss2</i> and <i>Ace2</i> are highly expressed in GI tissues with significant covariation. We identified a significant expression quantitative trait locus on chromosome 7 that controls the expression of both <i>Tmprss2</i> and <i>Ace2</i>. <i>Dhx32</i> was found to be the strongest candidate in this interval. Co-expression network analysis demonstrated that both <i>Tmprss2</i> and <i>Ace2</i> were located at the same module that is significantly associated with other GI-related traits. Protein–protein interaction analysis indicated that hub genes in this module are linked to circadian rhythms. Collectively, our data suggested that genes with circadian rhythms of expression may have an impact on COVID-19 disease, with implications related to the timing and treatment of COVID-19.Fuyi XuJun GaoBuyan-Ochir OrgilAkhilesh Kumar BajpaiQingqing GuEnkhsaikhan PurevjavAthena S. DavenportKui LiJeffrey A. TowbinDennis D. BlackJoseph F. PierreLu LuMDPI AGarticleBXD micegastrointestinal tracttranscriptomeco-expressionCOVID-19SARS-CoV-2MedicineRENJournal of Personalized Medicine, Vol 11, Iss 1212, p 1212 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	BXD mice gastrointestinal tract transcriptome co-expression COVID-19 SARS-CoV-2 Medicine R
spellingShingle	BXD mice gastrointestinal tract transcriptome co-expression COVID-19 SARS-CoV-2 Medicine R Fuyi Xu Jun Gao Buyan-Ochir Orgil Akhilesh Kumar Bajpai Qingqing Gu Enkhsaikhan Purevjav Athena S. Davenport Kui Li Jeffrey A. Towbin Dennis D. Black Joseph F. Pierre Lu Lu <i>Ace2</i> and <i>Tmprss2</i> Expressions Are Regulated by <i>Dhx32</i> and Influence the Gastrointestinal Symptoms Caused by SARS-CoV-2
description	Studies showed that the gastrointestinal (GI) tract is one of the most important pathways for SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19). As SARS-CoV-2 cellular entry depends on the ACE2 receptor and TMPRSS2 priming of the spike protein, it is important to understand the molecular mechanisms through which these two proteins and their cognate transcripts interact and influence the pathogenesis of COVID-19. In this study, we quantified the expression, associations, genetic modulators, and molecular pathways for <i>Tmprss2</i> and <i>Ace2</i> mRNA expressions in GI tissues using a systems genetics approach and the expanded family of highly diverse BXD mouse strains. The results showed that both <i>Tmprss2</i> and <i>Ace2</i> are highly expressed in GI tissues with significant covariation. We identified a significant expression quantitative trait locus on chromosome 7 that controls the expression of both <i>Tmprss2</i> and <i>Ace2</i>. <i>Dhx32</i> was found to be the strongest candidate in this interval. Co-expression network analysis demonstrated that both <i>Tmprss2</i> and <i>Ace2</i> were located at the same module that is significantly associated with other GI-related traits. Protein–protein interaction analysis indicated that hub genes in this module are linked to circadian rhythms. Collectively, our data suggested that genes with circadian rhythms of expression may have an impact on COVID-19 disease, with implications related to the timing and treatment of COVID-19.
format	article
author	Fuyi Xu Jun Gao Buyan-Ochir Orgil Akhilesh Kumar Bajpai Qingqing Gu Enkhsaikhan Purevjav Athena S. Davenport Kui Li Jeffrey A. Towbin Dennis D. Black Joseph F. Pierre Lu Lu
author_facet	Fuyi Xu Jun Gao Buyan-Ochir Orgil Akhilesh Kumar Bajpai Qingqing Gu Enkhsaikhan Purevjav Athena S. Davenport Kui Li Jeffrey A. Towbin Dennis D. Black Joseph F. Pierre Lu Lu
author_sort	Fuyi Xu
title	<i>Ace2</i> and <i>Tmprss2</i> Expressions Are Regulated by <i>Dhx32</i> and Influence the Gastrointestinal Symptoms Caused by SARS-CoV-2
title_short	<i>Ace2</i> and <i>Tmprss2</i> Expressions Are Regulated by <i>Dhx32</i> and Influence the Gastrointestinal Symptoms Caused by SARS-CoV-2
title_full	<i>Ace2</i> and <i>Tmprss2</i> Expressions Are Regulated by <i>Dhx32</i> and Influence the Gastrointestinal Symptoms Caused by SARS-CoV-2
title_fullStr	<i>Ace2</i> and <i>Tmprss2</i> Expressions Are Regulated by <i>Dhx32</i> and Influence the Gastrointestinal Symptoms Caused by SARS-CoV-2
title_full_unstemmed	<i>Ace2</i> and <i>Tmprss2</i> Expressions Are Regulated by <i>Dhx32</i> and Influence the Gastrointestinal Symptoms Caused by SARS-CoV-2
title_sort	<i>ace2</i> and <i>tmprss2</i> expressions are regulated by <i>dhx32</i> and influence the gastrointestinal symptoms caused by sars-cov-2
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c76ba44428a94ab795261a539ab9c493
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<i>Ace2</i> and <i>Tmprss2</i> Expressions Are Regulated by <i>Dhx32</i> and Influence the Gastrointestinal Symptoms Caused by SARS-CoV-2

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