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Chaotic activation of developmental signalling pathways drives idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is characterised by an important remodelling of lung parenchyma. Current evidence indicates that the disease is triggered by alveolar epithelium activation following chronic lung injury, resulting in alveolar epithelial type 2 cell hyperplasia and bronchiolisation...

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Autores principales: Froidure, Antoine, Marchal-Duval, Emmeline, Homps-Legrand, Meline, Ghanem, Mada, Justet, Aurélien, Crestani, Bruno, Mailleux, Arnaud
Formato: Online Artículo Texto
Lenguaje:English
Publicado: European Respiratory Society 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9488512/
https://www.ncbi.nlm.nih.gov/pubmed/33208483
http://dx.doi.org/10.1183/16000617.0140-2019
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author Froidure, Antoine
Marchal-Duval, Emmeline
Homps-Legrand, Meline
Ghanem, Mada
Justet, Aurélien
Crestani, Bruno
Mailleux, Arnaud
author_facet Froidure, Antoine
Marchal-Duval, Emmeline
Homps-Legrand, Meline
Ghanem, Mada
Justet, Aurélien
Crestani, Bruno
Mailleux, Arnaud
author_sort Froidure, Antoine
collection PubMed
description Idiopathic pulmonary fibrosis (IPF) is characterised by an important remodelling of lung parenchyma. Current evidence indicates that the disease is triggered by alveolar epithelium activation following chronic lung injury, resulting in alveolar epithelial type 2 cell hyperplasia and bronchiolisation of alveoli. Signals are then delivered to fibroblasts that undergo differentiation into myofibroblasts. These changes in lung architecture require the activation of developmental pathways that are important regulators of cell transformation, growth and migration. Among others, aberrant expression of profibrotic Wnt-β-catenin, transforming growth factor-β and Sonic hedgehog pathways in IPF fibroblasts has been assessed. In the present review, we will discuss the transcriptional integration of these different pathways during IPF as compared with lung early ontogeny. We will challenge the hypothesis that aberrant transcriptional integration of these pathways might be under the control of a chaotic dynamic, meaning that a small change in baseline conditions could be sufficient to trigger fibrosis rather than repair in a chronically injured lung. Finally, we will discuss some potential opportunities for treatment, either by suppressing deleterious mechanisms or by enhancing the expression of pathways involved in lung repair. Whether developmental mechanisms are involved in repair processes induced by stem cell therapy will also be discussed.
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spelling pubmed-94885122022-11-14 Chaotic activation of developmental signalling pathways drives idiopathic pulmonary fibrosis Froidure, Antoine Marchal-Duval, Emmeline Homps-Legrand, Meline Ghanem, Mada Justet, Aurélien Crestani, Bruno Mailleux, Arnaud Eur Respir Rev Reviews Idiopathic pulmonary fibrosis (IPF) is characterised by an important remodelling of lung parenchyma. Current evidence indicates that the disease is triggered by alveolar epithelium activation following chronic lung injury, resulting in alveolar epithelial type 2 cell hyperplasia and bronchiolisation of alveoli. Signals are then delivered to fibroblasts that undergo differentiation into myofibroblasts. These changes in lung architecture require the activation of developmental pathways that are important regulators of cell transformation, growth and migration. Among others, aberrant expression of profibrotic Wnt-β-catenin, transforming growth factor-β and Sonic hedgehog pathways in IPF fibroblasts has been assessed. In the present review, we will discuss the transcriptional integration of these different pathways during IPF as compared with lung early ontogeny. We will challenge the hypothesis that aberrant transcriptional integration of these pathways might be under the control of a chaotic dynamic, meaning that a small change in baseline conditions could be sufficient to trigger fibrosis rather than repair in a chronically injured lung. Finally, we will discuss some potential opportunities for treatment, either by suppressing deleterious mechanisms or by enhancing the expression of pathways involved in lung repair. Whether developmental mechanisms are involved in repair processes induced by stem cell therapy will also be discussed. European Respiratory Society 2020-11-18 /pmc/articles/PMC9488512/ /pubmed/33208483 http://dx.doi.org/10.1183/16000617.0140-2019 Text en Copyright ©ERS 2020. https://creativecommons.org/licenses/by-nc/4.0/This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.
spellingShingle Reviews
Froidure, Antoine
Marchal-Duval, Emmeline
Homps-Legrand, Meline
Ghanem, Mada
Justet, Aurélien
Crestani, Bruno
Mailleux, Arnaud
Chaotic activation of developmental signalling pathways drives idiopathic pulmonary fibrosis
title Chaotic activation of developmental signalling pathways drives idiopathic pulmonary fibrosis
title_full Chaotic activation of developmental signalling pathways drives idiopathic pulmonary fibrosis
title_fullStr Chaotic activation of developmental signalling pathways drives idiopathic pulmonary fibrosis
title_full_unstemmed Chaotic activation of developmental signalling pathways drives idiopathic pulmonary fibrosis
title_short Chaotic activation of developmental signalling pathways drives idiopathic pulmonary fibrosis
title_sort chaotic activation of developmental signalling pathways drives idiopathic pulmonary fibrosis
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9488512/
https://www.ncbi.nlm.nih.gov/pubmed/33208483
http://dx.doi.org/10.1183/16000617.0140-2019
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