RT Journal Article
T1 TGF-β antagonist attenuates fibrosis but not luminal narrowing in experimental tracheal stenosis
A1 Antón-Pacheco Sánchez, Juan Luis
A1 Usategui, Alicia
A1 Martínez, Ivám
A1 García Herrero, Carmen M.
A1 Gámez García, Antonio Pablo
A1 Grau, Montserrat
A1 Martinez, Ana M.
A1 Rodríguez Peralto, José Luis
A1 Pablos Álvarez, José Luis
AB Objective: Acquired tracheal stenosis (ATS) is an unusual disease often secondary to prolonged mechanical trauma. Acquired tracheal stenosis pathogenesis involves inflammation and subsequent fibrosis with narrowing of the tracheal lumen. Transforming growth factor-β1 (TGF-β) represents a pivotal factor in most fibrotic processes, and therefore a potential target in this context. The aim of this study is to analyze the role of TGF-β as a target for anti-fibrotic interventions in tracheal stenosis.Methods: Human stenotic tracheobronchial tissues from patients with benign airway stenosis and normal controls from pneumonectomy specimens were analyzed. Tracheal stenosis was induced in adult NZ rabbits by a circumferential thermal injury to the mucosa during open surgery and re-anastomosis. Rabbits were treated postoperatively with a peritracheal collagen sponge containing a TGF-β peptide antagonist (p17) or vehicle. Fibrosis was determined by Masson's trichrome staining, and smooth muscle cell α-actin+ (α-SMA+ Confirm accuracy.) myofibroblasts, connective tissue growth factor (CTGF), and p-Smad2/3 expression by immunohistochemistry.Results: Human and rabbit stenotic tissues showed extensive submucosal fibrosis, characterized by significantly increased α-SMA+ myofibroblasts and CTGF expression. In human stenotic lesions, increased p-Smad2/3+ nuclei were also observed. p17 treatment significantly reduced the fibrotic thickness, as well as the density of α-SMA+ myofibroblasts and CTGF+ cells in rabbit stenotic lesions, but failed to improve the luminal area.Conclusion: ATS is characterized by a TGF-β dependent fibrotic process, but reduction of the fibrotic component by TGF-β1 antagonist therapy was not sufficient to improve tracheal narrowing, suggesting that fibrosis may not be the main contributor to luminal stenosis.
PB Wiley
SN 0023-852X
YR 2017
FD 2017-02-22
LK https://hdl.handle.net/20.500.14352/113656
UL https://hdl.handle.net/20.500.14352/113656
LA eng
NO Antón-Pacheco, J.L., Usategui, A., Martínez, I., García-Herrero, C.M., Gamez, A.P., Grau, M., Martínez, A.M., Rodríguez-Peralto, J.L. and Pablos, J.L. (2017), TGF-β antagonist attenuates fibrosis but not luminal narrowing in experimental tracheal stenosis. The Laryngoscope, 127: 561-567.
NO Instituto de Salud Carlos III
NO Unión Europea
DS Docta Complutense
RD 26 abr 2025