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Rapamycin inhibits human laryngotracheal stenosis-derived fibroblast proliferation, metabolism, and function in vitro.


ABSTRACT: To determine if rapamycin inhibits the growth, function, and metabolism of human laryngotracheal stenosis (LTS)-derived fibroblasts.Controlled in vitro study.Tertiary care hospital in a research university.Fibroblasts isolated from biopsies of 5 patients with laryngotracheal stenosis were cultured. Cell proliferation, histology, gene expression, and cellular metabolism of LTS-derived fibroblasts were assessed in 4 conditions: (1) fibroblast growth medium, (2) fibroblast growth medium with dimethylsulfoxide (DMSO), (3) fibroblast growth medium with 10(-10) M (low-dose) rapamycin dissolved in DMSO, and (4) fibroblast growth medium with 10(-9) M (high-dose) rapamycin dissolved in DMSO.The LTS fibroblast count and DNA concentration were reduced after treatment with high-dose rapamycin compared to DMSO (P = .0007) and normal (P = .0007) controls. Collagen I expression decreased after treatment with high-dose rapamycin versus control (P = .0051) and DMSO (P = .0093) controls. Maximal respiration decreased to 68.6 pMoles of oxygen/min/10 mg/protein from 96.9 for DMSO (P = .0002) and 97.0 for normal (P = .0022) controls. Adenosine triphosphate (ATP) production decreased to 66.8 pMoles from 88.1 for DMSO (P = .0006) and 83.3 for normal (P = .0003) controls. Basal respiration decreased to 78.6 pMoles from 108 for DMSO (P = .0002) and 101 for normal (P = .0014) controls.Rapamycin demonstrated an anti-fibroblast 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's anti-fibroblast effects indicate a promising adjuvant therapy for the treatment of laryngotracheal stenosis.

SUBMITTER: Namba DR 

PROVIDER: S-EPMC4648293 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Rapamycin inhibits human laryngotracheal stenosis-derived fibroblast proliferation, metabolism, and function in vitro.

Namba Daryan R DR   Ma Garret G   Samad Idris I   Ding Dacheng D   Pandian Vinciya V   Powell Jonathan D JD   Horton Maureen R MR   Hillel Alexander T AT  

Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery 20150309 5


<h4>Objective</h4>To determine if rapamycin inhibits the growth, function, and metabolism of human laryngotracheal stenosis (LTS)-derived fibroblasts.<h4>Study design</h4>Controlled in vitro study.<h4>Setting</h4>Tertiary care hospital in a research university.<h4>Subjects and methods</h4>Fibroblasts isolated from biopsies of 5 patients with laryngotracheal stenosis were cultured. Cell proliferation, histology, gene expression, and cellular metabolism of LTS-derived fibroblasts were assessed in  ...[more]

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