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Multiple Expression Assessments of ACE2 and TMPRSS2 SARS-CoV-2 Entry Molecules in the Urinary Tract and Their Associations with Clinical Manifestations of COVID-19

BACKGROUND: Since December 2019, the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first spread quickly in Wuhan, China, then globally. Based on previously published evidence, ACE2 and TMPRSS2 are both pivotal entry molecules that enable cellular infection by SARS-...

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Autores principales: Ren, Xiaohan, Wang, Shangqian, Chen, Xinglin, Wei, Xiyi, Li, Guangyao, Ren, Shancheng, Zhang, Tongtong, Zhang, Xu, Lu, Zhongwen, You, Zebing, Wang, Zengjun, Song, Ninghong, Qin, Chao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650837/
https://www.ncbi.nlm.nih.gov/pubmed/33177848
http://dx.doi.org/10.2147/IDR.S270543
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author Ren, Xiaohan
Wang, Shangqian
Chen, Xinglin
Wei, Xiyi
Li, Guangyao
Ren, Shancheng
Zhang, Tongtong
Zhang, Xu
Lu, Zhongwen
You, Zebing
Wang, Zengjun
Song, Ninghong
Qin, Chao
author_facet Ren, Xiaohan
Wang, Shangqian
Chen, Xinglin
Wei, Xiyi
Li, Guangyao
Ren, Shancheng
Zhang, Tongtong
Zhang, Xu
Lu, Zhongwen
You, Zebing
Wang, Zengjun
Song, Ninghong
Qin, Chao
author_sort Ren, Xiaohan
collection PubMed
description BACKGROUND: Since December 2019, the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first spread quickly in Wuhan, China, then globally. Based on previously published evidence, ACE2 and TMPRSS2 are both pivotal entry molecules that enable cellular infection by SARS-CoV-2. Also, increased expression of pro-inflammatory cytokines, or a “cytokine storm,” is associated with multiple organ dysfunction syndrome often observed in critically ill patients. METHODS: We investigated the expression pattern of ACE2 and TMPRSS2 in major organs in the human body, especially in specific disease conditions. Multiple sequence alignment of ACE2 in different species was used to explain animal susceptibility. Moreover, the cell-specific expression patterns of ACE2 and cytokine receptors in the urinary tract were assessed using single-cell RNA sequencing (scRNA-seq). Additional biological relevance was determined through Gene Set Enrichment Analysis (GSEA) using an ACE2-specific signature. RESULTS: Our results revealed that ACE2 and TMPRSS2 were highly expressed in genitourinary organs. ACE2 was highly and significantly expressed in the kidney among individuals with chronic kidney diseases or diabetic nephropathy. In single cells, ACE2 was primarily enriched in gametocytes in the testis and renal proximal tubules. The receptors for pro-inflammatory cytokines, especially IL6ST, were notably concentrated in endothelial cells, macrophages, spermatogonial stem cells in the testis, and renal endothelial cells, which suggested the occurrence of alternative damaging autoimmune mechanisms. CONCLUSION: This study provided new insights into the pathogenic mechanisms of SARS-CoV-2 that underlie the clinical manifestations observed in the human testis and kidney. These observations might substantially facilitate the development of effective treatments for this rapidly spreading disease.
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spelling pubmed-76508372020-11-10 Multiple Expression Assessments of ACE2 and TMPRSS2 SARS-CoV-2 Entry Molecules in the Urinary Tract and Their Associations with Clinical Manifestations of COVID-19 Ren, Xiaohan Wang, Shangqian Chen, Xinglin Wei, Xiyi Li, Guangyao Ren, Shancheng Zhang, Tongtong Zhang, Xu Lu, Zhongwen You, Zebing Wang, Zengjun Song, Ninghong Qin, Chao Infect Drug Resist Original Research BACKGROUND: Since December 2019, the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first spread quickly in Wuhan, China, then globally. Based on previously published evidence, ACE2 and TMPRSS2 are both pivotal entry molecules that enable cellular infection by SARS-CoV-2. Also, increased expression of pro-inflammatory cytokines, or a “cytokine storm,” is associated with multiple organ dysfunction syndrome often observed in critically ill patients. METHODS: We investigated the expression pattern of ACE2 and TMPRSS2 in major organs in the human body, especially in specific disease conditions. Multiple sequence alignment of ACE2 in different species was used to explain animal susceptibility. Moreover, the cell-specific expression patterns of ACE2 and cytokine receptors in the urinary tract were assessed using single-cell RNA sequencing (scRNA-seq). Additional biological relevance was determined through Gene Set Enrichment Analysis (GSEA) using an ACE2-specific signature. RESULTS: Our results revealed that ACE2 and TMPRSS2 were highly expressed in genitourinary organs. ACE2 was highly and significantly expressed in the kidney among individuals with chronic kidney diseases or diabetic nephropathy. In single cells, ACE2 was primarily enriched in gametocytes in the testis and renal proximal tubules. The receptors for pro-inflammatory cytokines, especially IL6ST, were notably concentrated in endothelial cells, macrophages, spermatogonial stem cells in the testis, and renal endothelial cells, which suggested the occurrence of alternative damaging autoimmune mechanisms. CONCLUSION: This study provided new insights into the pathogenic mechanisms of SARS-CoV-2 that underlie the clinical manifestations observed in the human testis and kidney. These observations might substantially facilitate the development of effective treatments for this rapidly spreading disease. Dove 2020-11-04 /pmc/articles/PMC7650837/ /pubmed/33177848 http://dx.doi.org/10.2147/IDR.S270543 Text en © 2020 Ren et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Ren, Xiaohan
Wang, Shangqian
Chen, Xinglin
Wei, Xiyi
Li, Guangyao
Ren, Shancheng
Zhang, Tongtong
Zhang, Xu
Lu, Zhongwen
You, Zebing
Wang, Zengjun
Song, Ninghong
Qin, Chao
Multiple Expression Assessments of ACE2 and TMPRSS2 SARS-CoV-2 Entry Molecules in the Urinary Tract and Their Associations with Clinical Manifestations of COVID-19
title Multiple Expression Assessments of ACE2 and TMPRSS2 SARS-CoV-2 Entry Molecules in the Urinary Tract and Their Associations with Clinical Manifestations of COVID-19
title_full Multiple Expression Assessments of ACE2 and TMPRSS2 SARS-CoV-2 Entry Molecules in the Urinary Tract and Their Associations with Clinical Manifestations of COVID-19
title_fullStr Multiple Expression Assessments of ACE2 and TMPRSS2 SARS-CoV-2 Entry Molecules in the Urinary Tract and Their Associations with Clinical Manifestations of COVID-19
title_full_unstemmed Multiple Expression Assessments of ACE2 and TMPRSS2 SARS-CoV-2 Entry Molecules in the Urinary Tract and Their Associations with Clinical Manifestations of COVID-19
title_short Multiple Expression Assessments of ACE2 and TMPRSS2 SARS-CoV-2 Entry Molecules in the Urinary Tract and Their Associations with Clinical Manifestations of COVID-19
title_sort multiple expression assessments of ace2 and tmprss2 sars-cov-2 entry molecules in the urinary tract and their associations with clinical manifestations of covid-19
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650837/
https://www.ncbi.nlm.nih.gov/pubmed/33177848
http://dx.doi.org/10.2147/IDR.S270543
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