In:
The Laryngoscope, Wiley, Vol. 131, No. 9 ( 2021-09)
Abstract:
Tracheal stenosis is an obstructive disease of the upper airway that commonly develops as a result of abnormal wound healing. We evaluated the anti‐inflammatory and antifibrotic properties of nintedanib on tracheal stenosis both in vitro and in vivo. Study Design Prospective controlled animal study and in vitro comparative study of human cells. Methods An animal model of tracheal stenosis was induced via tracheal trauma. Postsurgical rats were orally administered with nintedanib (10 or 20 mg/kg/d) or saline (negative control) for 2 weeks, and tracheal specimens were harvested after 3 weeks. Degree of stenosis, collagen deposition, fibrotic surrogate markers expression, and T‐lymphocytic infiltration were evaluated. Human fetal lung fibroblast‐1 (HFL‐1) cells were cultured to determine the effects of nintedanib on changes of cellular biological function induced by transforming growth factor‐β1 (TGF‐β1). Results Rat tracheal stenotic tissues exhibited thickened lamina propria with irregular epithelium, characterized by significantly increased collagen deposition and elevated TGF‐β1, collagen I, α‐SMA and fibronectin expressions. Nintedanib markedly attenuated the tracheal stenotic lesions, reduced the collagen deposition and the expression of fibrotic marker proteins, and mitigated CD4+ T‐lymphocyte infiltration. Additionally, cellular proliferation and migration were decreased dose‐dependently in TGF‐β1‐stimulated HFL‐1 cells when treated with nintedanib. Furthermore, nintedanib inhibited TGF‐β1‐induced HFL‐1 differentiation and reduced the mRNA levels of the profibrotic genes. TGF‐β1‐activated phosphorylation of the TGF‐β/Smad2/3 and ERK1/2 pathways were also blocked by nintedanib. Conclusion Nintedanib effectively prevented tracheal stenosis in rats by inhibiting fibrosis and inflammation. The antifibrotic effect of nintedanib may be achieved by inhibiting fibroblasts' proliferation, migration and differentiation and suppressing the TGF‐β1/Smad2/3 and ERK1/2 signaling pathways. Level of Evidence NA Laryngoscope , 131:E2496–E2505, 2021
Type of Medium:
Online Resource
ISSN:
0023-852X
,
1531-4995
Language:
English
Publisher:
Wiley
Publication Date:
2021
detail.hit.zdb_id:
2026089-1
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