Enhanced endogenous bone morphogenetic protein signaling protects against bleomycin induced pulmonary fibrosis - Université de Lorraine Accéder directement au contenu
Article Dans Une Revue Respiratory Research Année : 2015

Enhanced endogenous bone morphogenetic protein signaling protects against bleomycin induced pulmonary fibrosis

Résumé

Background: Effective treatments for fibrotic diseases such as idiopathic pulmonary fibrosis are largely lacking. Transforming growth factor beta (TGFβ) plays a central role in the pathophysiology of fibrosis. We hypothesized that bone morphogenetic proteins (BMP), another family within the TGFβ superfamily of growth factors, modulate fibrogenesis driven by TGFβ. We therefore studied the role of endogenous BMP signaling in bleomycin induced lung fibrosis. Methods: Lung fibrosis was induced in wild-type or noggin haploinsufficient (Nog +/LacZ ) mice by intratracheal instillation of bleomycin, or phosphate buffered saline as a control. Invasive pulmonary function tests were performed using the flexiVent® SCIREQ system. The mice were sacrificed and lung tissue was collected for analysis using histopathology, collagen quantification, immunohistochemistry and gene expression analysis. Results: Nog +/LacZ mice are a known model of increased BMP signaling and were partially protected from bleomycin-induced lung fibrosis with reduced Ashcroft score, reduced collagen content and preservation of pulmonary compliance. In bleomycin-induced lung fibrosis, TGFβ and BMP signaling followed an inverse course, with dynamic activation of TGFβ signaling and repression of BMP signaling activity. Conclusions: Upon bleomycin exposure, active BMP signaling is decreased. Derepression of BMP signaling in Nog +/LacZ mice protects against bleomycin-induced pulmonary fibrosis. Modulating the balance between BMP and TGFβ, in particular increasing endogenous BMP signals, may therefore be a therapeutic target in fibrotic lung disease.
Fichier principal
Vignette du fichier
s12931-015-0202-x.pdf (2.09 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Loading...

Dates et versions

hal-01704505 , version 1 (15-02-2018)

Identifiants

Citer

Ellen de Langhe, Frederic Cailotto, Vanessa de Vooght, Carolina Aznar-Lopez, Jeroen Alfons Vanoirbeek, et al.. Enhanced endogenous bone morphogenetic protein signaling protects against bleomycin induced pulmonary fibrosis. Respiratory Research, 2015, 16 (1), pp.38. ⟨10.1186/s12931-015-0202-x⟩. ⟨hal-01704505⟩

Collections

UNIV-LORRAINE
48 Consultations
66 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More