{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T06:47:31Z","timestamp":1770706051860,"version":"3.49.0"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,2,18]],"date-time":"2019-02-18T00:00:00Z","timestamp":1550448000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Idiopathic subglottic stenosis (iSGS) is commonly characterized by laryngeal fibrosis thought to arise by epithelia\u2010mesenchymal transition (EMT) induced by chronic inflammation. Pepsin is a potent inducer of inflammation in the airways during chronic laryngopharyngeal reflux and has been observed in the subglottic mucosa of patients with iSGS, absent in normal mucosa. The aim of this study was to examine the effect of pepsin on mechanisms of EMT in laryngeal cells with implications for iSGS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>In vitro translational research study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human laryngeal epithelial cell cultures were exposed to 0.1\u2009mg\/mL or 1.0\u2009mg\/mL pepsin at pH7 for 24 and 48\u2009hours, or media pH5\u2009\u00b1\u20090.1\u2009mg\/mL pepsin for 10\u2009minutes and harvested after 24 and 48\u2009hours. EMT marker expression was measured by qPCR and enzyme\u2010linked immunosorbent assays. Wound\u2010healing scratch assay was performed on immortalized human vocal fold fibroblasts pretreated with media pH5\u2009\u00b1\u20090.1\u2009mg\/mL pepsin (10\u2009minutes) or continuously treated with media pH7\u2009\u00b1\u20090.1 to 1\u2009mg\/mL pepsin for 24\u2009hours.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Pepsin yielded no effect on <jats:italic>MMP1, MMP9, FN1, COL1A1, HAS2<\/jats:italic>, or <jats:italic>CDH1<\/jats:italic> gene expression or matrix metalloproteinase\u20109 or fibronectin protein expression, either alone or in the presence of weak acid. Pepsin and\/or acid produced no effect on fibroblast migration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Whereas pepsin has been shown to be present in the subglottic mucosa of patients with iSGS, this in vitro acute exposure investigation does not provide evidence of a direct causal role for development of fibrosis in subglottic epithelial cell cultures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Levels of Evidence<\/jats:title><jats:p>NA. <jats:italic>Laryngoscope<\/jats:italic>, 130:154\u2013158, 2020<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.27879","type":"journal-article","created":{"date-parts":[[2019,2,18]],"date-time":"2019-02-18T15:33:37Z","timestamp":1550504017000},"page":"154-158","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["The role of pepsin in epithelia\u2010mesenchymal transition in idiopathic subglottic 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