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A New Model of Acute Exacerbation of Experimental Pulmonary Fibrosis in Mice
Rationale: idiopathic pulmonary fibrosis (IPF) is the most severe form of fibrosing interstitial lung disease, characterized by progressive respiratory failure leading to death. IPF’s natural history is heterogeneous, and its progression unpredictable. Most patients develop a progressive decline of...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9654438/ https://www.ncbi.nlm.nih.gov/pubmed/36359778 http://dx.doi.org/10.3390/cells11213379 |
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author | Yegen, Céline-Hivda Haine, Liasmine Da Costa Ferreira, Kevin Marchant, Dominique Bernaudin, Jean-Francois Planès, Carole Voituron, Nicolas Boncoeur, Emilie |
author_facet | Yegen, Céline-Hivda Haine, Liasmine Da Costa Ferreira, Kevin Marchant, Dominique Bernaudin, Jean-Francois Planès, Carole Voituron, Nicolas Boncoeur, Emilie |
author_sort | Yegen, Céline-Hivda |
collection | PubMed |
description | Rationale: idiopathic pulmonary fibrosis (IPF) is the most severe form of fibrosing interstitial lung disease, characterized by progressive respiratory failure leading to death. IPF’s natural history is heterogeneous, and its progression unpredictable. Most patients develop a progressive decline of respiratory function over years; some remain stable, but others present a fast-respiratory deterioration without identifiable cause, classified as acute exacerbation (AE). Objectives: to develop and characterize an experimental mice model of lung fibrosis AE, mimicking IPF-AE at the functional, histopathological, cellular and molecular levels. Methods: we established in C57BL/6 male mice a chronic pulmonary fibrosis using a repetitive low-dose bleomycin (BLM) intratracheal (IT) instillation regimen (four instillations of BLM every 2 weeks), followed by two IT instillations of a simple or double-dose BLM challenge to induce AE. Clinical follow-up and histological and molecular analyses were done for fibrotic and inflammatory lung remodeling analysis. Measurements and main results: as compared with a low-dose BLM regimen, this AE model induced a late burst of animal mortality, worsened lung fibrosis and remodeling, and superadded histopathological features as observed in humans IPF-AE. This was associated with stronger inflammation, increased macrophage infiltration of lung tissue and increased levels of pro-inflammatory cytokines in lung homogenates. Finally, it induced in the remodeled lung a diffuse expression of hypoxia-inducible factor 1α, a hallmark of tissular hypoxia response and a major player in the progression of IPF. Conclusion: this new model is a promising model of AE in chronic pulmonary fibrosis that could be relevant to mimic IPF-AE in preclinical trials. |
format | Online Article Text |
id | pubmed-9654438 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96544382022-11-15 A New Model of Acute Exacerbation of Experimental Pulmonary Fibrosis in Mice Yegen, Céline-Hivda Haine, Liasmine Da Costa Ferreira, Kevin Marchant, Dominique Bernaudin, Jean-Francois Planès, Carole Voituron, Nicolas Boncoeur, Emilie Cells Article Rationale: idiopathic pulmonary fibrosis (IPF) is the most severe form of fibrosing interstitial lung disease, characterized by progressive respiratory failure leading to death. IPF’s natural history is heterogeneous, and its progression unpredictable. Most patients develop a progressive decline of respiratory function over years; some remain stable, but others present a fast-respiratory deterioration without identifiable cause, classified as acute exacerbation (AE). Objectives: to develop and characterize an experimental mice model of lung fibrosis AE, mimicking IPF-AE at the functional, histopathological, cellular and molecular levels. Methods: we established in C57BL/6 male mice a chronic pulmonary fibrosis using a repetitive low-dose bleomycin (BLM) intratracheal (IT) instillation regimen (four instillations of BLM every 2 weeks), followed by two IT instillations of a simple or double-dose BLM challenge to induce AE. Clinical follow-up and histological and molecular analyses were done for fibrotic and inflammatory lung remodeling analysis. Measurements and main results: as compared with a low-dose BLM regimen, this AE model induced a late burst of animal mortality, worsened lung fibrosis and remodeling, and superadded histopathological features as observed in humans IPF-AE. This was associated with stronger inflammation, increased macrophage infiltration of lung tissue and increased levels of pro-inflammatory cytokines in lung homogenates. Finally, it induced in the remodeled lung a diffuse expression of hypoxia-inducible factor 1α, a hallmark of tissular hypoxia response and a major player in the progression of IPF. Conclusion: this new model is a promising model of AE in chronic pulmonary fibrosis that could be relevant to mimic IPF-AE in preclinical trials. MDPI 2022-10-26 /pmc/articles/PMC9654438/ /pubmed/36359778 http://dx.doi.org/10.3390/cells11213379 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yegen, Céline-Hivda Haine, Liasmine Da Costa Ferreira, Kevin Marchant, Dominique Bernaudin, Jean-Francois Planès, Carole Voituron, Nicolas Boncoeur, Emilie A New Model of Acute Exacerbation of Experimental Pulmonary Fibrosis in Mice |
title | A New Model of Acute Exacerbation of Experimental Pulmonary Fibrosis in Mice |
title_full | A New Model of Acute Exacerbation of Experimental Pulmonary Fibrosis in Mice |
title_fullStr | A New Model of Acute Exacerbation of Experimental Pulmonary Fibrosis in Mice |
title_full_unstemmed | A New Model of Acute Exacerbation of Experimental Pulmonary Fibrosis in Mice |
title_short | A New Model of Acute Exacerbation of Experimental Pulmonary Fibrosis in Mice |
title_sort | new model of acute exacerbation of experimental pulmonary fibrosis in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9654438/ https://www.ncbi.nlm.nih.gov/pubmed/36359778 http://dx.doi.org/10.3390/cells11213379 |
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