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2017 ; 127
(3
): E107-E113
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Metabolic variations in normal and fibrotic human laryngotracheal-derived
fibroblasts: A Warburg-like effect
#MMPMID27585358
Ma G
; Samad I
; Motz K
; Yin LX
; Duvvuri MV
; Ding D
; Namba DR
; Elisseeff JH
; Horton MR
; Hillel AT
Laryngoscope
2017[Mar]; 127
(3
): E107-E113
PMID27585358
show ga
OBJECTIVES/HYPOTHESIS: 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.
STUDY DESIGN: In vitro comparative analysis. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. LEVEL OF EVIDENCE: NA Laryngoscope, 127:E107-E113, 2017.