期刊
LARYNGOSCOPE
卷 131, 期 7, 页码 E2125-E2130出版社
WILEY
DOI: 10.1002/lary.29385
关键词
Laryngotracheal stenosis; DON; fibrosis; glutamine; glutaminase
资金
- National Institute on Deafness and Other Communication Disorders of the National Institutes of Health [1R01DC018567, 1K23DC014082, R21DC017225]
- Triological Society
The study demonstrates that broadly active glutamine antagonist DON significantly reduces fibrosis in iLTS mice. These results suggest that glutamine inhibition may be a therapeutic option to reduce fibrosis in laryngotracheal stenosis.
Objective/Hypothesis Glutamine inhibition has been demonstrated an antifibrotic effect in iatrogenic laryngotracheal stenosis (iLTS) scar fibroblasts in vitro. We hypothesize that broadly active glutamine antagonist, DON will reduce collagen formation and fibrosis-associated gene expression in iLTS mice. Study Design Prospective controlled animal study. Methods iLTS in mice were induced by chemomechanical injury of the trachea using a bleomycin-coated wire brush. PBS or DON (1.3 mg/kg) were administered by intraperitoneal injection (i.p.) every other day. Laryngotracheal complexes were harvested at days 7 and 14 after the initiation of DON treatment for the measurement of lamina propria thickness, trichrome stain, immunofluorescence staining of collagen 1, and fibrosis-associated gene expression. Results The study demonstrated that DON treatment reduced lamina propria thickness (P = .025) and collagen formation in trichrome stain and immunofluorescence staining of collagen 1. In addition, DON decreased fibrosis-associated gene expression in iLTS mice. At day 7, DON inhibited Col1a1 (P < .0001), Col3a1 (P = .0046), Col5a1 (P < .0001), and Tgf beta (P = .023) expression. At day 14, DON reduced Co1a1 (P = .0076) and Tgf beta (P = .023) expression. Conclusions Broadly active glutamine antagonist, DON, significantly reduces fibrosis in iLTS mice. These results suggest that the concept of glutamine inhibition may be a therapeutic option to reduce fibrosis in the laryngotracheal stenosis. Level of Evidence N/A Laryngoscope, 2021
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据