title: Metabolic variations in normal and fibrotic human laryngotracheal-derived fibroblasts: A Warburg-like effect.
abstract: Laryngotracheal stenosis (LTS) is a chronic fibrotic disease characterized by fibroblast proliferation, collagen deposition, and matrix remodeling in the lamina propria of the larynx and/or trachea. Current medical therapies are limited by a poor understanding of the effector cell's (fibroblasts) cellular biology and metabolism. The purpose of this study was to compare cellular proliferation, function, and metabolism between normal and LTS-derived fibroblasts in vitro. We hypothesize that LTS-derived fibroblasts will demonstrate aberrant behavior with faster proliferation, increased collagen production, and altered metabolic allocation compared with normal fibroblasts.
  
  
  
  In vitro comparative analysis.
  
  
  
  Human biopsies of normal and iatrogenic LTS tissue (n = 7) were obtained, and fibroblasts were isolated and cultured in vitro. Cellular proliferation, cellular histology, gene expression, and metabolic analyses were performed. Statistical analyses comparing normal and scar-derived fibroblasts were performed.
  
  
  
  LTS fibroblast proliferation rate, cellular surface area, and collagen-1 expression were increased compared to normal fibroblasts. Cellular metabolic analysis of LTS-derived fibroblasts demonstrated reduced oxidative phosphorylation and increased glycolysis/oxidative phosphorylation ratio compared with normal fibroblasts.
  
  
  
  Human iatrogenic LTS-derived fibroblasts demonstrated aberrant behavior when compared with normal fibroblasts. A Warburg-like effect was revealed, suggesting human iatrogenic LTS fibroblasts drive their proliferation with aerobic glycolysis. The distinct metabolism suggests metabolic inhibitors could reduce fibroblast hyperplasia and hypertrophy in LTS and fibrosis in general.
  
  
  
  NA Laryngoscope, 127:E107-E113, 2017.
authors: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.
authors: Garret
authors: G
authors: Ma
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.
authors: Idris
authors: I
authors: Samad
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.
authors: Kevin
authors: K
authors: Motz
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.
authors: Linda X
authors: LX
authors: Yin
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.
authors: Madhavi V
authors: MV
authors: Duvvuri
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.
authors: Dacheng
authors: D
authors: Ding
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.
authors: Daryan R
authors: DR
authors: Namba
authors: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.
authors: Jennifer H
authors: JH
authors: Elisseeff
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.
authors: Maureen R
authors: MR
authors: Horton
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.
authors: Alexander T
authors: AT
authors: Hillel
mesh_terms: D001707:Biopsy, Needle; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007829:Laryngostenosis / Q000378:metabolism / Q000473:pathology*; D010101:Oxygen Consumption; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012016:Reference Values; D012494:Sampling Studies; D018709:Statistics, Nonparametric; D014135:Tracheal Stenosis / Q000378:metabolism / Q000473:pathology*
chemical_list: D003094:Collagen
keywords: Fibrosis; Warburg effect; cellular metabolism; fibroblasts; laryngotracheal stenosis; larynx; mechanistic target of rapamycin