The role of nicotinic receptors in SARS-CoV-2 receptor ACE2 expression in intestinal epithelia
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Bioelectronic Medicine
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The role of nicotinic receptors in SARS-CoV-2 receptor ACE2 expression in intestinal epithelia Anne S. ten Hove1 , David J. Brinkman1,2, Andrew Y. F. Li Yim1,3, Caroline Verseijden1, Theo B. M. Hakvoort1, Iris Admiraal1, Olaf Welting1, Patricia H. P. van Hamersveld1, Valérie Sinniger4, Bruno Bonaz4, Misha D. Luyer2 and Wouter J. de Jonge1,5*
Abstract 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 coexpressed 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
Background Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), is characterized by a vast release of cytokines. * Correspondence: [email protected] 1 Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, University of Amsterdam, Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam 1105 BK, the Netherlands 5 Department of General, Visceral-, Thoracic and Vascular Surgery, University Hospital Bonn, 53127 Bonn, Germany Full list of author information is available at the end of the article
Aggravated by following sepsis, this was established to be the cause of death in 28% of the infected patients (Zhang et al. 2020). At the time of writing this manuscript, no cure nor vaccine exists yet and hence, many studies investigating treatment options have been initiated. Amongst these, vagus nerve stimulation (VNS) has been put forward as potential therapy because of its abil
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