{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T17:07:46Z","timestamp":1793207266958,"version":"4.5.0"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,3,9]],"date-time":"2015-03-09T00:00:00Z","timestamp":1425859200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["aao-hnsfjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Otolaryngol.--head neck surg."],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine if rapamycin inhibits the growth, function, and metabolism of human laryngotracheal stenosis (LTS)\u2013derived fibroblasts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>Controlled in vitro study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Tertiary care hospital in a research university.<\/jats:p><\/jats:sec><jats:sec><jats:title>Subjects and Methods<\/jats:title><jats:p>Fibroblasts isolated from biopsies of 5 patients with laryngotracheal stenosis were cultured. Cell proliferation, histology, gene expression, and cellular metabolism of LTS\u2010derived fibroblasts were assessed in 4 conditions: (1) fibroblast growth medium, (2) fibroblast growth medium with dimethylsulfoxide (DMSO), (3) fibroblast growth medium with 10<jats:sup>\u221210<\/jats:sup> M (low\u2010dose) rapamycin dissolved in DMSO, and (4) fibroblast growth medium with 10<jats:sup>\u22129<\/jats:sup> M (high\u2010dose) rapamycin dissolved in DMSO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The LTS fibroblast count and DNA concentration were reduced after treatment with high\u2010dose rapamycin compared to DMSO (<jats:italic>P<\/jats:italic> =. 0007) and normal (<jats:italic>P<\/jats:italic> =. 0007) controls. Collagen I expression decreased after treatment with high\u2010dose rapamycin versus control (<jats:italic>P<\/jats:italic> =. 0051) and DMSO (<jats:italic>P<\/jats:italic> =. 0093) controls. Maximal respiration decreased to 68.6 pMoles of oxygen\/min\/10\u00a0mg\/protein from 96.9 for DMSO (<jats:italic>P<\/jats:italic> =. 0002) and 97.0 for normal (<jats:italic>P<\/jats:italic> =. 0022) controls. Adenosine triphosphate (ATP) production decreased to 66.8 pMoles from 88.1 for DMSO (<jats:italic>P<\/jats:italic> =. 0006) and 83.3 for normal (<jats:italic>P<\/jats:italic> =. 0003) controls. Basal respiration decreased to 78.6 pMoles from 108 for DMSO (<jats:italic>P<\/jats:italic> =. 0002) and 101 for normal (<jats:italic>P<\/jats:italic> =. 0014) controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Rapamycin demonstrated an anti\u2010fibroblast effect by significantly reducing the proliferation, metabolism, and collagen deposition of human LTS fibroblast in vitro. Rapamycin significantly decreased oxidative phosphorylation of LTS fibroblasts, suggesting at a potential mechanism for the reduced proliferation and differentiation. Furthermore, rapamycin\u2019s anti\u2010fibroblast effects indicate a promising adjuvant therapy for the treatment of laryngotracheal stenosis.<\/jats:p><\/jats:sec>","DOI":"10.1177\/0194599815573708","type":"journal-article","created":{"date-parts":[[2015,3,9]],"date-time":"2015-03-09T21:52:30Z","timestamp":1425937950000},"page":"881-888","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Rapamycin Inhibits Human Laryngotracheal Stenosis\u2013derived Fibroblast Proliferation, Metabolism, and Function in Vitro"],"prefix":"10.1002","volume":"152","author":[{"given":"Daryan R.","family":"Namba","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garret","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Biomedical 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