Rapamycin Inhibits Human Laryngotracheal Stenosis–derived Fibroblast Proliferation, Metabolism, and Function in Vitro
| Autor: | Daryan R. Namba, Jonathan D. Powell, Alexander T. Hillel, Idris Samad, Dacheng Ding, Vinciya Pandian, Garret Ma, Maureen R. Horton |
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| Rok vydání: | 2015 |
| Předmět: |
Pathology
medicine.medical_specialty Cell Culture Techniques Biology Real-Time Polymerase Chain Reaction Article chemistry.chemical_compound Gene expression medicine Humans Fibroblast Cell Proliferation Sirolimus Growth medium Cell growth Laryngostenosis Fibroblasts Molecular biology In vitro medicine.anatomical_structure Real-time polymerase chain reaction Otorhinolaryngology chemistry Cell culture Surgery Collagen Immunosuppressive Agents medicine.drug |
| Zdroj: | Otolaryngology–Head and Neck Surgery. 152:881-888 |
| ISSN: | 1097-6817 0194-5998 |
| DOI: | 10.1177/0194599815573708 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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