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Inhibition of glutaminase to reverse fibrosis in iatrogenic laryngotracheal stenosis

The Laryngoscope Jan 14, 2020

Tsai HW, Motz KM, Ding D, et al. - Given the significance of glutamine metabolism as an energy source for iatrogenic laryngotracheal stenosis (iLTS) scar fibroblasts, and importance of the enzyme, glutaminase (GLS), for converting glutamine to glutamate, researchers designed test-tube Lab Research to investigate their hypothesis that the GLS-specific inhibitor BPTES will block glutaminolysis and decrease iLTS scar fibroblast proliferation, collagen deposition, and fibroblast metabolism in vitro. GLS expression was determined via assessment of immunohistochemistry of a cricotracheal resection (n = 1) and a normal airway specimen (n = 1). From patients with iLTS (n = 6), brush biopsies of subglottic/tracheal fibrosis and normal airway were assessed for GLS expression. From biopsies of subglottic/tracheal fibrosis (n = 6), fibroblasts were isolated and cultured. They treated fibroblasts with BPTES and BPTES + dimethyl α-ketoglutarate (DMK), an analog of the downstream product of GLS. The outcomes revealed overexpression of GLS in iLTS scar. iLTS scar fibroblasts proliferation and function inhibit significantly with blockage of GLS with BPTES, showing a critical role for GLS in iLTS. Hence a successful strategy to reverse scar formation in the airway suggested in this work is targeting GLS to inhibit glutaminolysis.
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