title: TGF-β antagonist attenuates fibrosis but not luminal narrowing in experimental tracheal stenosis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  NA. Laryngoscope, 127:561-567, 2017.
authors.affiliation: Servicio de Cirugía Pediátrica, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Juan L
authors.initials: JL
authors.lastname: Antón-Pacheco
authors.affiliation: Grupo de Enfermedades Inflamatorias y Autoinmunes, Instituto de Investigación Hospital 12 de Octubre (Imas12), Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Usategui
authors.affiliation: Servicio de Cirugía Torácica, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Iván
authors.initials: I
authors.lastname: Martínez
authors.affiliation: Grupo de Enfermedades Inflamatorias y Autoinmunes, Instituto de Investigación Hospital 12 de Octubre (Imas12), Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Carmen M
authors.initials: CM
authors.lastname: García-Herrero
authors.affiliation: Servicio de Cirugía Torácica, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Antonio P
authors.initials: AP
authors.lastname: Gamez
authors.affiliation: Unidad de Animalario y Quirófanos Experimentales, Instituto de Investigación Hospital 12 de Octubre (Imas12), Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Grau
authors.affiliation: Universidad Francisco de Vitoria, Facultad de Ciencias Sanitarias, Escuela de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.|Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Martínez
authors.affiliation: Servicio de Anatomía Patológica, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Rodríguez-Peralto
authors.affiliation: Grupo de Enfermedades Inflamatorias y Autoinmunes, Instituto de Investigación Hospital 12 de Octubre (Imas12), Universidad Complutense de Madrid, Madrid, Spain.|Servicio de Reumatología, Hospital 12 de Octubre, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Pablos
mesh_terms: D000293:Adolescent; D000818:Animals; D001707:Biopsy, Needle; D002648:Child; D015331:Cohort Studies; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011817:Rabbits; D012016:Reference Values; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D046509:Tissue Culture Techniques; D014135:Tracheal Stenosis / Q000188:drug therapy* / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016212:Transforming Growth Factor beta
keywords: TGF-β antagonist; Tracheal stenosis; animal model