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

Bioelectronic Medicine

Misha D. Luyer¹  Valérie Sinniger²  Bruno Bonaz²  Theo B. M. Hakvoort³  Iris Admiraal³  Olaf Welting³  Anne S. ten Hove³  Caroline Verseijden³  Patricia H. P. van Hamersveld³  Andrew Y. F. Li Yim⁴  Wouter J. de Jonge⁵  David J. Brinkman⁶ 

[1] Department of Surgery, Catharina Hospital, 5623 EJ, Eindhoven, the Netherlands;Grenoble Institute of Neurosciences, Division of Hepato-Gastroenterology, University Grenoble Alpes, Inserm U1216, 38000, Grenoble, France;Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, University of Amsterdam, Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, 1105 BK, Amsterdam, the Netherlands;Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, University of Amsterdam, Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, 1105 BK, Amsterdam, the Netherlands;Department of Clinical Genetics, Genome Diagnostics Laboratory, Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ, Amsterdam, the Netherlands;Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, University of Amsterdam, Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, 1105 BK, Amsterdam, the Netherlands;Department of General, Visceral-, Thoracic and Vascular Surgery, University Hospital Bonn, 53127, Bonn, Germany;Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, University of Amsterdam, Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, 1105 BK, Amsterdam, the Netherlands;Department of Surgery, Catharina Hospital, 5623 EJ, Eindhoven, the Netherlands;

关键词: Vagus nerve stimulation;    nAChR;    COVID-19;    SARS-CoV-2;    ACE2;    TMPRSS2;   

DOI  :  10.1186/s42234-020-00057-1

来源: Springer

【 摘 要 】

BackgroundRecent 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.MethodsBy 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.ResultsWe 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.ConclusionsACE2 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.

【 授权许可】

CC BY