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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2017

Open Access 01-12-2017 | Research

BDNF/TrkB axis activation promotes epithelial–mesenchymal transition in idiopathic pulmonary fibrosis

Authors: Emanuela Cherubini, Salvatore Mariotta, Davide Scozzi, Rita Mancini, Giorgia Osman, Michela D’Ascanio, Pierdonato Bruno, Giuseppe Cardillo, Alberto Ricci

Published in: Journal of Translational Medicine | Issue 1/2017

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Abstract

Background

Neurotrophins (NT) belongs to a family of growth factors which promotes neurons survival and differentiation. Increasing evidence show that NT and their receptor are expressed in lung tissues suggesting a possible role in lung health and disease. Here we investigated the expression and functional role of the TrkB/BDNF axis in idiopathic pulmonary fibrotic lung (myo)fibroblasts.

Methods

Lung fibroblast were isolated from IPF patients and characterized for the expression of mesenchymal markers in comparison to normal lung fibroblasts isolated from non-IPF controls.

Results

BDNF treatment promoted mesenchymal differentiation and this effect was counteracted by the TrkB inhibitor K252a. In this regard, we showed that K252a treatment was able to control the expression of transcription factors involved in epithelial to mesenchymal transition (EMT). Accordingly, K252a treatment reduced matrix metalloproteinase-9 enzyme activity and E-cadherin expression while increased cytoplasmic β-catenin expression.

Conclusions

Our results suggest that BDNF/TrkB axis plays a role in EMT promoting the acquisition of (myo)fibroblast cell phenotype in IPF. Targeting BDNF/TrkB seems to represent a viable approach in order to prevent EMT dependent lung fibrosis.
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Metadata
Title
BDNF/TrkB axis activation promotes epithelial–mesenchymal transition in idiopathic pulmonary fibrosis
Authors
Emanuela Cherubini
Salvatore Mariotta
Davide Scozzi
Rita Mancini
Giorgia Osman
Michela D’Ascanio
Pierdonato Bruno
Giuseppe Cardillo
Alberto Ricci
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2017
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-017-1298-1

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