https://scholars.lib.ntu.edu.tw/handle/123456789/592641| Title: | ACE2 localizes to the respiratory cilia and is not increased by ACE inhibitors or ARBs | Authors: | Lee I.T. Nakayama T. Wu C.-T. Goltsev Y. Jiang S. Gall P.A. Liao C.-K. Shih L.-C. Schürch C.M. McIlwain D.R. Chu P. Borchard N.A. Zarabanda D. Dholakia S.S. Yang A. Kim D. Chen H. Kanie T. Lin C.-D. Tsai M.-H. Phillips K.M. Kim R. Overdevest J.B. Tyler M.A. Yan C.H. Lin C.-F. Lin Y.-T. Bau D.-T. Tsay G.J. Patel Z.M. Tsou Y.-A. Tzankov A. Matter M.S. Tai C.-J. TE-HUEI YEH Hwang P.H. Nolan G.P. Nayak J.V. Jackson P.K. |
Issue Date: | 2020 | Publisher: | Nature Research | Journal Volume: | 11 | Journal Issue: | 1 | Source: | Nature Communications | Abstract: | The coronavirus SARS-CoV-2 is the causative agent of the ongoing severe acute respiratory disease pandemic COVID-19. Tissue and cellular tropism is one key to understanding the pathogenesis of SARS-CoV-2. We investigate the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of human donors using a diverse panel of banked tissues. Here, we report our discovery that the ACE2 receptor protein robustly localizes within the motile cilia of airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during host respiratory transmission. We further determine whether ciliary ACE2 expression in the upper airway is influenced by patient demographics, clinical characteristics, comorbidities, or medication use, and show the first mechanistic evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) does not increase susceptibility to SARS-CoV-2 infection through enhancing the expression of ciliary ACE2 receptor. These findings are crucial to our understanding of the transmission of SARS-CoV-2 for prevention and control of this virulent pathogen. ? 2020, The Author(s). |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85094215416&doi=10.1038%2fs41467-020-19145-6&partnerID=40&md5=fc587aba86fd7c368aaea2fbe85ce6e6 https://scholars.lib.ntu.edu.tw/handle/123456789/592641 |
ISSN: | 2041-1723 | DOI: | 10.1038/s41467-020-19145-6 | SDG/Keyword: | angiotensin converting enzyme 2; angiotensin receptor antagonist; dipeptidyl carboxypeptidase inhibitor; messenger RNA; mucin 5AC; receptor protein; angiotensin converting enzyme 2; angiotensin receptor antagonist; dipeptidyl carboxypeptidase; dipeptidyl carboxypeptidase inhibitor; cell; ciliate; disease transmission; gene expression; inhibitor; pathogenicity; protein; respiratory disease; viral disease; adult; aged; airway epithelium cell; animal cell; animal experiment; Article; cellular distribution; clinical article; clinical feature; comorbidity; controlled study; coronavirus disease 2019; enzyme localization; female; gene expression; human; human cell; human tissue; infection control; infection prevention; infection sensitivity; male; motile cilium; mouse; nonhuman; nose; pandemic; protein expression; respiratory system; Severe acute respiratory syndrome coronavirus 2; upper respiratory tract; virus cell interaction; virus entry; virus transmission; age; cilium; Coronavirus infection; drug effect; endothelium cell; genetics; goblet cell; lung; metabolism; pathology; respiratory system; sex factor; sinusitis; smoking; virology; virus pneumonia; Coronavirus; SARS coronavirus; Age Factors; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cilia; Coronavirus Infections; Endothelial Cells; Gene Expression; Goblet Cells; Humans; Lung; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Respiratory System; Sex Factors; Sinusitis; Smoking [SDGs]SDG3 |
| Appears in Collections: | 醫學院附設醫院 (臺大醫院) |
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