TGF-β antagonist attenuates fibrosis but not luminal narrowing in experimental tracheal stenosis.
Autor: Antón-Pacheco, Juan L.; Usategui, Alicia; Martínez, Iván; García-Herrero, Carmen M.; Gamez, Antonio P.; Grau, Montserrat; Martínez Relimpio, Ana María; Rodríguez-Peralto, José L.; Pablos, José L.
Resumen: Introduction/Objective: Acquired tracheal stenosis (ATS) is an unusual disease
often secondary to prolonged mechanical trauma. ATS pathogenesis involves
inflammation and subsequent fibrosis with narrowing of the tracheal lumen. 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 α-SMA+
Results: Human and rabbit stenotic tissues showed extensive submucosal fibrosis,
characterized by significantly increased α-SMA
myofibroblasts, CTGF and p-Smad2/3 expression by
immunohistochemistry.
+ 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+
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.
cells in rabbit stenotic lesions but failed
to improve the luminal area.
Identificador universal: http://hdl.handle.net/10641/1248
Fecha: 2016
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