{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T23:48:55Z","timestamp":1787874535729,"version":"build-2784847793"},"reference-count":31,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T00:00:00Z","timestamp":1598572800000},"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":[[2021,7]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Iatrogenic laryngotracheal stenosis (iLTS) is the pathological narrowing of the glottis, subglottis, and\/or trachea due to scar tissue. Patients with type 2 diabetes mellitus (T2DM) are over 8 times more likely to develop iLTS and represent 26% to 53% of all iLTS patients. In this investigation, we compared iLTS scar\u2010derived fibroblasts in patients with and without T2DM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>Controlled ex vivo study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>iLTS scar fibroblasts were isolated and cultured from subglottic scar biopsies in iLTS patients diagnosed with or without type 2 diabetes (non\u2010T2DM). Fibroblast proliferation, fibrosis\u2010related gene expression, and metabolic utilization of oxidative phosphorylation (OXPHOS) and glycolysis were assessed. Contractility was measured using a collagen\u2010based assay. Metabolically targeted drugs (metformin, phenformin, amobarbital) were tested, and changes in fibrosis\u2010related gene expression, collagen protein, and contractility were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to non\u2010T2DM, T2DM iLTS scar fibroblasts had increased \u03b1\u2010smooth muscle actin (\u03b1SMA) expression (8.2\u00d7 increased, <jats:italic>P<\/jats:italic>\u00a0=\u2009.020), increased contractility (mean 71.4 \u00b1\u20094.3% vs. 51.7 \u00b1\u200916% \u0394 area \u00d7\u200990\u2009minute<jats:sup>\u22121<\/jats:sup>, <jats:italic>P<\/jats:italic>\u00a0=\u2009.016), and reduced proliferation (1.9\u00d7 reduction at 5\u2009days, <jats:italic>P<\/jats:italic>\u00a0&lt;\u2009.01). Collagen 1 (COL1) protein was significantly higher in the T2DM group (mean 2.06 \u00b1\u20090.19 vs. 0.74 \u00b1.44 COL1\/total protein [pg\/\u03bcg], <jats:italic>P<\/jats:italic>\u00a0=\u2009.036). T2DM iLTS scar fibroblasts had increased measures of OXPHOS, including basal respiration (mean 86.7 vs. 31.5 pmol\/minute\/10 \u03bcg protein, <jats:italic>P<\/jats:italic>\u00a0=\u2009.016) and adenosine triphosphate (ATP) generation (mean 97.5 vs. 25.7 pmol\/minute\/10 \u03bcg protein, <jats:italic>P<\/jats:italic>\u00a0=\u2009.047) compared to non\u2010T2DM fibroblasts. Amobarbital reduced cellular contractility; decreased collagen protein; and decreased expression of \u03b1SMA, COL1, and fibronectin. Metformin and phenformin did not significantly affect fibrosis\u2010related gene expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>T2DM iLTS scar fibroblasts demonstrate a myofibroblast phenotype and greater contractility compared to non\u2010T2DM. Their bioenergetic preference for OXPHOS drives their increased contractility, which is selectively targeted by amobarbital.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>NA <jats:italic>Laryngoscope<\/jats:italic>, 131:1570\u20131577, 2021<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.29026","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T22:44:25Z","timestamp":1598654665000},"page":"1570-1577","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Characterization of Fibroblasts in Iatrogenic Laryngotracheal Stenosis and Type <scp>II<\/scp> Diabetes Mellitus"],"prefix":"10.1002","volume":"131","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8619-7312","authenticated-orcid":false,"given":"Ioan","family":"Lina","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Johns Hopkins Medical Institutions  Baltimore Maryland U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiu\u2010Wen","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Johns Hopkins Medical Institutions  Baltimore Maryland U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dacheng","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Johns Hopkins Medical Institutions  Baltimore Maryland U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9592-932X","authenticated-orcid":false,"given":"Ruth","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Johns Hopkins Medical Institutions  Baltimore Maryland U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9255-7265","authenticated-orcid":false,"given":"Kevin M.","family":"Motz","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Johns Hopkins Medical Institutions  Baltimore Maryland U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8471-5449","authenticated-orcid":false,"given":"Alexander T.","family":"Hillel","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Johns Hopkins Medical Institutions  Baltimore Maryland 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