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The role of nicotinic receptors in SARS-CoV-2 receptor ACE2 expression in intestinal epithelia

BACKGROUND: Recent evidence demonstrated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) propagates in intestinal epithelial cells expressing Angiotensin-Converting Enzyme 2 (ACE2), implying that these cells represent an important entry site for the viral infection. Nicotinic recep...

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Autores principales: ten Hove, Anne S., Brinkman, David J., Li Yim, Andrew Y. F., Verseijden, Caroline, Hakvoort, Theo B. M., Admiraal, Iris, Welting, Olaf, van Hamersveld, Patricia H. P., Sinniger, Valérie, Bonaz, Bruno, Luyer, Misha D., de Jonge, Wouter J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592135/
https://www.ncbi.nlm.nih.gov/pubmed/33123616
http://dx.doi.org/10.1186/s42234-020-00057-1
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author ten Hove, Anne S.
Brinkman, David J.
Li Yim, Andrew Y. F.
Verseijden, Caroline
Hakvoort, Theo B. M.
Admiraal, Iris
Welting, Olaf
van Hamersveld, Patricia H. P.
Sinniger, Valérie
Bonaz, Bruno
Luyer, Misha D.
de Jonge, Wouter J.
author_facet ten Hove, Anne S.
Brinkman, David J.
Li Yim, Andrew Y. F.
Verseijden, Caroline
Hakvoort, Theo B. M.
Admiraal, Iris
Welting, Olaf
van Hamersveld, Patricia H. P.
Sinniger, Valérie
Bonaz, Bruno
Luyer, Misha D.
de Jonge, Wouter J.
author_sort ten Hove, Anne S.
collection PubMed
description BACKGROUND: Recent evidence demonstrated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) propagates in intestinal epithelial cells expressing Angiotensin-Converting Enzyme 2 (ACE2), implying that these cells represent an important entry site for the viral infection. Nicotinic receptors (nAChRs) have been put forward as potential regulators of inflammation and of ACE2 expression. As vagus nerve stimulation (VNS) activates nAChRs, we aimed to investigate whether VNS can be instrumental in affecting intestinal epithelial ACE2 expression. METHODS: By using publicly available datasets we qualified epithelial ACE2 expression in human intestine, and assessed gene co-expression of ACE2 and SARS-CoV-2 priming Transmembrane Serine Protease 2 (TMPRSS2) with nAChRs in intestinal epithelial cells. Next, we investigated mouse and human ACE2 expression in intestinal tissues after chronic VNS via implanted devices. RESULTS: We show co-expression of ACE2 and TMPRSS2 with nAChRs and α7 nAChR in particular in intestinal stem cells, goblet cells, and enterocytes. However, VNS did not affect ACE2 expression in murine or human intestinal tissue, albeit in colitis setting. CONCLUSIONS: ACE2 and TMPRSS2 are specifically expressed in epithelial cells of human intestine, and both are co-expressed with nAChRs. However, no evidence for regulation of ACE2 expression through VNS could be found. Hence, a therapeutic value of VNS with respect to SARS-CoV-2 infection risk through ACE2 receptor modulation in intestinal epithelia could not be established.
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spelling pubmed-75921352020-10-28 The role of nicotinic receptors in SARS-CoV-2 receptor ACE2 expression in intestinal epithelia ten Hove, Anne S. Brinkman, David J. Li Yim, Andrew Y. F. Verseijden, Caroline Hakvoort, Theo B. M. Admiraal, Iris Welting, Olaf van Hamersveld, Patricia H. P. Sinniger, Valérie Bonaz, Bruno Luyer, Misha D. de Jonge, Wouter J. Bioelectron Med Short Report BACKGROUND: Recent evidence demonstrated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) propagates in intestinal epithelial cells expressing Angiotensin-Converting Enzyme 2 (ACE2), implying that these cells represent an important entry site for the viral infection. Nicotinic receptors (nAChRs) have been put forward as potential regulators of inflammation and of ACE2 expression. As vagus nerve stimulation (VNS) activates nAChRs, we aimed to investigate whether VNS can be instrumental in affecting intestinal epithelial ACE2 expression. METHODS: By using publicly available datasets we qualified epithelial ACE2 expression in human intestine, and assessed gene co-expression of ACE2 and SARS-CoV-2 priming Transmembrane Serine Protease 2 (TMPRSS2) with nAChRs in intestinal epithelial cells. Next, we investigated mouse and human ACE2 expression in intestinal tissues after chronic VNS via implanted devices. RESULTS: We show co-expression of ACE2 and TMPRSS2 with nAChRs and α7 nAChR in particular in intestinal stem cells, goblet cells, and enterocytes. However, VNS did not affect ACE2 expression in murine or human intestinal tissue, albeit in colitis setting. CONCLUSIONS: ACE2 and TMPRSS2 are specifically expressed in epithelial cells of human intestine, and both are co-expressed with nAChRs. However, no evidence for regulation of ACE2 expression through VNS could be found. Hence, a therapeutic value of VNS with respect to SARS-CoV-2 infection risk through ACE2 receptor modulation in intestinal epithelia could not be established. BioMed Central 2020-10-28 /pmc/articles/PMC7592135/ /pubmed/33123616 http://dx.doi.org/10.1186/s42234-020-00057-1 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Short Report
ten Hove, Anne S.
Brinkman, David J.
Li Yim, Andrew Y. F.
Verseijden, Caroline
Hakvoort, Theo B. M.
Admiraal, Iris
Welting, Olaf
van Hamersveld, Patricia H. P.
Sinniger, Valérie
Bonaz, Bruno
Luyer, Misha D.
de Jonge, Wouter J.
The role of nicotinic receptors in SARS-CoV-2 receptor ACE2 expression in intestinal epithelia
title The role of nicotinic receptors in SARS-CoV-2 receptor ACE2 expression in intestinal epithelia
title_full The role of nicotinic receptors in SARS-CoV-2 receptor ACE2 expression in intestinal epithelia
title_fullStr The role of nicotinic receptors in SARS-CoV-2 receptor ACE2 expression in intestinal epithelia
title_full_unstemmed The role of nicotinic receptors in SARS-CoV-2 receptor ACE2 expression in intestinal epithelia
title_short The role of nicotinic receptors in SARS-CoV-2 receptor ACE2 expression in intestinal epithelia
title_sort role of nicotinic receptors in sars-cov-2 receptor ace2 expression in intestinal epithelia
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592135/
https://www.ncbi.nlm.nih.gov/pubmed/33123616
http://dx.doi.org/10.1186/s42234-020-00057-1
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