{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T11:22:28Z","timestamp":1773746548732,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,3,28]],"date-time":"2017-03-28T00:00:00Z","timestamp":1490659200000},"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"}]}],"content-domain":{"domain":["aao-hnsfjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Otolaryngol.--head neck surg."],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To elucidate the role of hypoxia and inflammatory pathways in the pathogenesis of iatrogenic laryngotracheal stenosis (iLTS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>(1) Examination of mucosal surface gene expression in human iLTS. (2) In vitro comparison of normal and scar laryngotracheal fibroblasts under normoxic and hypoxic conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Tertiary care hospital in a research university (2012\u20102016).<\/jats:p><\/jats:sec><jats:sec><jats:title>Subjects and Methods<\/jats:title><jats:p>Brush biopsies were obtained from normal laryngotracheal tissue and scar in iLTS patients; gene expression was compared. Fibroblasts were isolated from normal and scarred trachea and grown in vitro in either a 1% O<jats:sub>2<\/jats:sub> or normoxic environment. Cell growth and gene and protein expression were compared. Statistical analysis utilized a multilevel mixed effects model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Expression of IL\u20106 (fold change = 2.8, <jats:italic>P<\/jats:italic> &lt;. 01), myofibroblast marker \u03b1SMA (fold change = 3.0, <jats:italic>P<\/jats:italic> =. 01), and MMP13 (fold change = 5.4, <jats:italic>P<\/jats:italic> =. 02) was significantly increased in scar biopsy samples as compared to normal. Under hypoxic conditions in vitro, normal laryngotracheal fibroblasts proliferated significantly faster (n = 8, <jats:italic>P<\/jats:italic> &lt;. 01 each day). Expression of IL\u20106 (n = 8, fold change = 2.6, <jats:italic>P<\/jats:italic> &lt;. 01) increased significantly after 12 hours under hypoxia. Expression of \u03b1SMA (n = 8, fold change= 2.0, <jats:italic>P<\/jats:italic> =. 03), COL1 (n = 8, fold change = 1.1, <jats:italic>P<\/jats:italic> =. 03), and MMP13 (n = 8, fold change = 1.6, <jats:italic>P<\/jats:italic> =. 01) increased significantly after 48 hours under hypoxia. Scar fibroblasts also proliferated significantly faster under hypoxic conditions but did not display the same expression profile.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Human iLTS scar has a myofibroblast phenotype. Under hypoxic conditions in vitro, normal laryngotracheal fibroblasts can transdifferentiate into a similar phenotype. These changes may be mediated by IL\u20106, a fibrosis\u2010related cytokine.<\/jats:p><\/jats:sec>","DOI":"10.1177\/0194599817697049","type":"journal-article","created":{"date-parts":[[2017,3,28]],"date-time":"2017-03-28T08:50:00Z","timestamp":1490691000000},"page":"886-892","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Fibroblasts in Hypoxic Conditions Mimic Laryngotracheal Stenosis"],"prefix":"10.1002","volume":"156","author":[{"given":"Linda X.","family":"Yin","sequence":"first","affiliation":[{"name":"Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin M.","family":"Motz","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery, Johns Hopkins Baltimore Maryland 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