Enhanced endogenous bone morphogenetic protein signaling protects against bleomycin induced pulmonary fibrosis - Université de Lorraine Access content directly
Journal Articles Respiratory Research Year : 2015

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

Abstract

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
Origin : Publisher files allowed on an open archive
Loading...

Dates and versions

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

Identifiers

Cite

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 View
70 Download

Altmetric

Share

Gmail Facebook X LinkedIn More