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Short report
Anne Sophie ten Hove
Tytgat Institute for Liver and Intestinal Research
Corresponding Author
ORCiD: https://orcid.org/0000-0002-5733-1746
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This work is licensed under a CC BY 4.0 License. Read Full License
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.
Keywords
vagus nerve stimulation, nAChR, COVID-19, SARS-CoV-2, ACE2, TMPRSS2
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CURRENT STATUS: Published
View the published article at Bioelectronic Medicine.
Version 2
Posted 28 Aug, 2020
No community comments so far
Editorial decision: Accept
On 09 Sep, 2020
Reviewer #2 agreed
On 07 Sep, 2020
Review #2 received
Received 07 Sep, 2020
Editor assigned
On 26 Aug, 2020
Reviewers invited
Invitations sent on 26 Aug, 2020
Reviewer #1 agreed
On 26 Aug, 2020
Review #1 received
Received 26 Aug, 2020
Submission checks complete
On 25 Aug, 2020
Editor invited
On 25 Aug, 2020
No comments provided
Editorial decision: Major revision
On 17 Aug, 2020
Review #3 received
Received 14 Aug, 2020
Reviewer #3 agreed
On 08 Aug, 2020
Review #1 received
Received 08 Aug, 2020
Review #2 received
Received 08 Aug, 2020
Reviewer #2 agreed
On 04 Aug, 2020
Reviewer #1 agreed
On 04 Aug, 2020
Reviewers invited
Invitations sent on 02 Aug, 2020
Editor assigned
On 31 Jul, 2020
Editor invited
On 30 Jul, 2020
Submission checks complete
On 28 Jul, 2020
First submitted
On 24 Jul, 2020
Metrics
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Learn more about our company.
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
See the published version of this preprint at Bioelectronic Medicine.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Short report
Anne Sophie ten Hove
Tytgat Institute for Liver and Intestinal Research
Corresponding Author
ORCiD: https://orcid.org/0000-0002-5733-1746
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Bioelectronic Medicine.
Version 2
Posted 28 Aug, 2020
No community comments so far
Editorial decision: Accept
On 09 Sep, 2020
Reviewer #2 agreed
On 07 Sep, 2020
Review #2 received
Received 07 Sep, 2020
Editor assigned
On 26 Aug, 2020
Reviewers invited
Invitations sent on 26 Aug, 2020
Reviewer #1 agreed
On 26 Aug, 2020
Review #1 received
Received 26 Aug, 2020
Submission checks complete
On 25 Aug, 2020
Editor invited
On 25 Aug, 2020
No comments provided
Editorial decision: Major revision
On 17 Aug, 2020
Review #3 received
Received 14 Aug, 2020
Reviewer #3 agreed
On 08 Aug, 2020
Review #1 received
Received 08 Aug, 2020
Review #2 received
Received 08 Aug, 2020
Reviewer #2 agreed
On 04 Aug, 2020
Reviewer #1 agreed
On 04 Aug, 2020
Reviewers invited
Invitations sent on 02 Aug, 2020
Editor assigned
On 31 Jul, 2020
Editor invited
On 30 Jul, 2020
Submission checks complete
On 28 Jul, 2020
First submitted
On 24 Jul, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Bioelectronic Medicine.
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.
Figure 1
Figure 2
Figure 3
Figure 4
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