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BDNF/TrkB axis activation promotes epithelial–mesenchymal transition in idiopathic pulmonary fibrosis
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 f...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610541/ https://www.ncbi.nlm.nih.gov/pubmed/28938915 http://dx.doi.org/10.1186/s12967-017-1298-1 |
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author | Cherubini, Emanuela Mariotta, Salvatore Scozzi, Davide Mancini, Rita Osman, Giorgia D’Ascanio, Michela Bruno, Pierdonato Cardillo, Giuseppe Ricci, Alberto |
author_facet | Cherubini, Emanuela Mariotta, Salvatore Scozzi, Davide Mancini, Rita Osman, Giorgia D’Ascanio, Michela Bruno, Pierdonato Cardillo, Giuseppe Ricci, Alberto |
author_sort | Cherubini, Emanuela |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5610541 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-56105412017-10-10 BDNF/TrkB axis activation promotes epithelial–mesenchymal transition in idiopathic pulmonary fibrosis Cherubini, Emanuela Mariotta, Salvatore Scozzi, Davide Mancini, Rita Osman, Giorgia D’Ascanio, Michela Bruno, Pierdonato Cardillo, Giuseppe Ricci, Alberto J Transl Med Research 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. BioMed Central 2017-09-22 /pmc/articles/PMC5610541/ /pubmed/28938915 http://dx.doi.org/10.1186/s12967-017-1298-1 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Cherubini, Emanuela Mariotta, Salvatore Scozzi, Davide Mancini, Rita Osman, Giorgia D’Ascanio, Michela Bruno, Pierdonato Cardillo, Giuseppe Ricci, Alberto BDNF/TrkB axis activation promotes epithelial–mesenchymal transition in idiopathic pulmonary fibrosis |
title | BDNF/TrkB axis activation promotes epithelial–mesenchymal transition in idiopathic pulmonary fibrosis |
title_full | BDNF/TrkB axis activation promotes epithelial–mesenchymal transition in idiopathic pulmonary fibrosis |
title_fullStr | BDNF/TrkB axis activation promotes epithelial–mesenchymal transition in idiopathic pulmonary fibrosis |
title_full_unstemmed | BDNF/TrkB axis activation promotes epithelial–mesenchymal transition in idiopathic pulmonary fibrosis |
title_short | BDNF/TrkB axis activation promotes epithelial–mesenchymal transition in idiopathic pulmonary fibrosis |
title_sort | bdnf/trkb axis activation promotes epithelial–mesenchymal transition in idiopathic pulmonary fibrosis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610541/ https://www.ncbi.nlm.nih.gov/pubmed/28938915 http://dx.doi.org/10.1186/s12967-017-1298-1 |
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