{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:49:55Z","timestamp":1790887795755,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In asthma, goblet cell numbers are increased within the airway epithelium, perpetuating the production of mucus that is more difficult to clear and results in airway mucus plugging. Notch1, Notch2, or Notch3, or a combination of these has been shown to influence the differentiation of airway epithelial cells. How the expression of specific Notch isoforms differs in fully differentiated adult asthmatic epithelium and whether Notch influences mucin production after differentiation is currently unknown. We aimed to quantify different Notch isoforms in the airway epithelium of individuals with severe asthma and to examine the impact of Notch signaling on mucin MUC5AC. Human lung sections and primary bronchial epithelial cells from individuals with and without asthma were used in this study. Primary bronchial epithelial cells were differentiated at the air\u2013liquid interface for 28 days. Notch isoform expression was analyzed by Taqman quantitative PCR. Immunohistochemistry was used to localize and quantify Notch isoforms in human airway sections. Notch signaling was inhibited in vitro using dibenzazepine or Notch3-specific siRNA, followed by analysis of MUC5AC. NOTCH3 was highly expressed in asthmatic airway epithelium compared with nonasthmatic epithelium. Dibenzazepine significantly reduced MUC5AC production in air\u2013liquid interface cultures of primary bronchial epithelial cells concomitantly with suppression of NOTCH3 intracellular domain protein. Specific knockdown using NOTCH3 siRNA recapitulated the dibenzazepine-induced reduction in MUC5AC. We demonstrate that NOTCH3 is a regulator of MUC5AC production. Increased NOTCH3 signaling in the asthmatic airway epithelium may therefore be an underlying driver of excess MUC5AC production.<\/jats:p>","DOI":"10.1165\/rcmb.2019-0069oc","type":"journal-article","created":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T14:35:06Z","timestamp":1578666906000},"page":"513-523","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":54,"title":["Blocking Notch3 Signaling Abolishes MUC5AC Production in Airway Epithelial Cells from Individuals with Asthma"],"prefix":"10.1093","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5751-7025","authenticated-orcid":false,"given":"Andrew T.","family":"Reid","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy"},{"name":"Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristy S.","family":"Nichol","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, and"},{"name":"School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Punnam","family":"Chander Veerati","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, and"},{"name":"School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Moheimani","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy"},{"name":"Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Kicic","sequence":"additional","affiliation":[{"name":"School of Paediatrics and Child Health"},{"name":"Telethon Kids Institute, and"},{"name":"Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia, Australia"},{"name":"Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia"},{"name":"Occupation and Environment, School of Public Health, Curtin University, Bentley, Western Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Stick","sequence":"additional","affiliation":[{"name":"School of Paediatrics and Child Health"},{"name":"Telethon Kids Institute, and"},{"name":"Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia, Australia"},{"name":"Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan W.","family":"Bartlett","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy"},{"name":"Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris L.","family":"Grainge","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, and"},{"name":"School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia"},{"name":"Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, New South Wales, Australia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A. B.","family":"Wark","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, and"},{"name":"School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia"},{"name":"Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, New South Wales, Australia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip M.","family":"Hansbro","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy"},{"name":"Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darryl A.","family":"Knight","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy"},{"name":"Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, and"},{"name":"Department of Anesthesiology, Pharmacology 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