ArticleThe Laryngoscope2020
Inhibition of glutaminase to reverse fibrosis in iatrogenic laryngotracheal stenosis.
Article in The Laryngoscope, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- The role of glutamine metabolism in the pathogenesis of idiopathic pulmonary fibrosis and its therapeutic potential.Frontiers in oncology · 2026Review
- Review
- A two-way street - cellular metabolism and myofibroblast contraction.NPJ Regenerative medicine · 2024Review
- Targeting Pulmonary Fibrosis by SLC1A5-Dependent Glutamine Transport Blockade.American journal of respiratory cell and molecular biology · 2023Article
- Tracheal microbiome and metabolome profiling in iatrogenic subglottic tracheal stenosis.BMC pulmonary medicine · 2023Article
- External beam radiotherapy inhibits stent related granulation hyperplasia in rabbit trachea.Scientific reports · 2023Article
- Identifying Phenotypically Distinct Fibroblast Subsets in Type 2 Diabetes-Associated Iatrogenic Laryngotracheal Stenosis.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2022Article
- [An updated review of the mechanism of fibrosis in acquired laryngotrachealstenosis].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2022Review
- Differential Metabotypes in Synovial Fibroblasts and Synovial Fluid in Hip Osteoarthritis Patients Support Inflammatory Responses.International journal of molecular sciences · 2022Article
- Roles of NRF2 in Fibrotic Diseases: From Mechanisms to Therapeutic Approaches.Frontiers in physiology · 2022Review
- Characterization of Fibroblasts in Iatrogenic Laryngotracheal Stenosis and Type II Diabetes Mellitus.The Laryngoscope · 2021Article
- Glutamine Inhibition Reduces Iatrogenic Laryngotracheal Stenosis.The Laryngoscope · 2021Article
- Regulation of Extracellular Matrix Production in Activated Fibroblasts: Roles of Amino Acid Metabolism in Collagen Synthesis.Frontiers in oncology · 2021Review
- Reduced Oxidative Phosphorylation and Increased Glycolysis in Human Glaucoma Lamina Cribrosa Cells.Investigative ophthalmology & visual science · 2020Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
objectives/hypothesisGlutamine metabolism is a critical energy source for iatrogenic laryngotracheal stenosis (iLTS) scar fibroblasts, and glutaminase (GLS) is an essential enzyme converting glutamine to glutamate. We hypothesize that the GLS-specific inhibitor BPTES will block glutaminolysis and reduce iLTS scar fibroblast proliferation, collagen deposition, and fibroblast metabolism in vitro. STUDY
designTest-tube Lab Research.
methodsImmunohistochemistry of a cricotracheal resection (n = 1) and a normal airway specimen (n = 1) were assessed for GLS expression. GLS expression was assessed in brush biopsies of subglottic/tracheal fibrosis and normal airway from patients with iLTS (n = 6). Fibroblasts were isolated and cultured from biopsies of subglottic/tracheal fibrosis (n = 6). Fibroblast were treated with BPTES and BPTES + dimethyl α-ketoglutarate (DMK), an analogue of the downstream product of GLS. Fibroblast proliferation, gene expression, protein production, and metabolism were assessed in all treatment conditions and compared to control.
resultsGLS was overexpressed in brush biopsies of iLTS scar specimens (P = .029) compared to normal controls. In vitro, BPTES inhibited iLTS scar fibroblast proliferation (P = .007), collagen I (Col I) (P < .0001), collagen III (P = .004), and α-smooth muscle actin (P = .0025) gene expression and protein production (P = .031). Metabolic analysis demonstrated that BPTES reduced glycolytic reserve (P = .007) but had no effects on mitochondrial oxidative phosphorylation. DMK rescued BPTES inhibition of Col I gene expression (P = .0018) and protein production (P = .021).
conclusionsGLS is overexpressed in iLTS scar. Blockage of GLS with BPTES significantly inhibits iLTS scar fibroblasts proliferation and function, demonstrating a critical role for GLS in iLTS. Targeting GLS to inhibit glutaminolysis may be a successful strategy to reverse scar formation in the airway. LEVEL OF EVIDENCE: NA Laryngoscope, 2020.
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