{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T03:57:20Z","timestamp":1785902240337,"version":"3.56.0"},"reference-count":32,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T00:00:00Z","timestamp":1610409600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["1K23DC014082"],"award-info":[{"award-number":["1K23DC014082"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["1R01DC018567"],"award-info":[{"award-number":["1R01DC018567"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["R21DC017225"],"award-info":[{"award-number":["R21DC017225"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:sec><jats:title>Objective\/Hypothesis<\/jats:title><jats:p>Glutamine inhibition has been demonstrated an antifibrotic effect in iatrogenic laryngotracheal stenosis (iLTS) scar fibroblasts in vitro. We hypothesize that broadly active glutamine antagonist, DON will reduce collagen formation and fibrosis\u2010associated gene expression in iLTS mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>Prospective controlled animal study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>iLTS in mice were induced by chemomechanical injury of the trachea using a bleomycin\u2010coated wire brush. PBS or DON (1.3\u2009mg\/kg) were administered by intraperitoneal injection (<jats:italic>i.p<\/jats:italic>.) every other day. Laryngotracheal complexes were harvested at days 7 and 14 after the initiation of DON treatment for the measurement of lamina propria thickness, trichrome stain, immunofluorescence staining of collagen 1, and fibrosis\u2010associated gene expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The study demonstrated that DON treatment reduced lamina propria thickness (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.025) and collagen formation in trichrome stain and immunofluorescence staining of collagen 1. In addition, DON decreased fibrosis\u2010associated gene expression in iLTS mice. At day 7, DON inhibited Col1a1 (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.0001), Col3a1 (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.0046), Col5a1 (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.0001), and Tgf\u03b2 (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.023) expression. At day 14, DON reduced Co1a1 (<jats:italic>P\u2009=<\/jats:italic>\u00a0.0076) and Tgf\u03b2 (<jats:italic>P\u2009=<\/jats:italic>\u00a0.023) expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Broadly active glutamine antagonist, DON, significantly reduces fibrosis in iLTS mice. These results suggest that the concept of glutamine inhibition may be a therapeutic option to reduce fibrosis in the laryngotracheal stenosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>N\/A <jats:italic>Laryngoscope<\/jats:italic>, 131:E2125\u2013E2130, 2021<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.29385","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T08:34:13Z","timestamp":1610699653000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Glutamine Inhibition Reduces Iatrogenic Laryngotracheal Stenosis"],"prefix":"10.1002","volume":"131","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2837-6769","authenticated-orcid":false,"given":"Hsiu\u2010Wen","family":"Tsai","sequence":"first","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery Johns Hopkins School of Medicine  Baltimore Maryland U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8619-7312","authenticated-orcid":false,"given":"Ioan","family":"Lina","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery Johns Hopkins School of Medicine  Baltimore Maryland U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin M","family":"Motz","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery Johns Hopkins School of Medicine  Baltimore Maryland U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam","family":"Chung","sequence":"additional","affiliation":[{"name":"Bloomberg Kimmel Institute for Cancer Immunotherapy and Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine  Baltimore Maryland U.S.A."},{"name":"Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering Johns Hopkins University  Baltimore Maryland U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dacheng","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery Johns Hopkins School of Medicine  Baltimore Maryland U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael K.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Communication State University of New York Upstate Medical University  Syracuse New York U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Feeley","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Widener University  Chester Pennsylvania U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer H.","family":"Elisseeff","sequence":"additional","affiliation":[{"name":"Bloomberg Kimmel Institute for Cancer Immunotherapy and 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