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Longitudinal micro-computed tomography-derived biomarkers quantify non-resolving lung fibrosis in a silicosis mouse model

In spite of many compounds identified as antifibrotic in preclinical studies, pulmonary fibrosis remains a life-threatening condition for which highly effective treatment is still lacking. Towards improving the success-rate of bench-to-bedside translation, we investigated in vivo µCT-derived biomark...

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Autores principales: Dekoster, Kaat, Decaesteker, Tatjana, Berghen, Nathalie, Van den Broucke, Sofie, Jonckheere, Anne-Charlotte, Wouters, Jens, Krouglov, Anton, Lories, Rik, De Langhe, Ellen, Hoet, Peter, Verbeken, Erik, Vanoirbeek, Jeroen, Vande Velde, Greetje
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527558/
https://www.ncbi.nlm.nih.gov/pubmed/32999350
http://dx.doi.org/10.1038/s41598-020-73056-6
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author Dekoster, Kaat
Decaesteker, Tatjana
Berghen, Nathalie
Van den Broucke, Sofie
Jonckheere, Anne-Charlotte
Wouters, Jens
Krouglov, Anton
Lories, Rik
De Langhe, Ellen
Hoet, Peter
Verbeken, Erik
Vanoirbeek, Jeroen
Vande Velde, Greetje
author_facet Dekoster, Kaat
Decaesteker, Tatjana
Berghen, Nathalie
Van den Broucke, Sofie
Jonckheere, Anne-Charlotte
Wouters, Jens
Krouglov, Anton
Lories, Rik
De Langhe, Ellen
Hoet, Peter
Verbeken, Erik
Vanoirbeek, Jeroen
Vande Velde, Greetje
author_sort Dekoster, Kaat
collection PubMed
description In spite of many compounds identified as antifibrotic in preclinical studies, pulmonary fibrosis remains a life-threatening condition for which highly effective treatment is still lacking. Towards improving the success-rate of bench-to-bedside translation, we investigated in vivo µCT-derived biomarkers to repeatedly quantify experimental silica-induced pulmonary fibrosis and assessed clinically relevant readouts up to several months after silicosis induction. Mice were oropharyngeally instilled with crystalline silica or saline and longitudinally monitored with respiratory-gated-high-resolution µCT to evaluate disease onset and progress using scan-derived biomarkers. At weeks 1, 5, 9 and 15, we assessed lung function, inflammation and fibrosis in subsets of mice in a cross-sectional manner. Silica-instillation increased the non-aerated lung volume, corresponding to onset and progression of inflammatory and fibrotic processes not resolving with time. Moreover, total lung volume progressively increased with silicosis. The volume of healthy, aerated lung first dropped then increased, corresponding to an acute inflammatory response followed by recovery into lower elevated aerated lung volume. Imaging results were confirmed by a significantly decreased Tiffeneau index, increased neutrophilic inflammation, increased IL-13, MCP-1, MIP-2 and TNF-α concentration in bronchoalveolar lavage fluid, increased collagen content and fibrotic nodules. µCT-derived biomarkers enable longitudinal evaluation of early onset inflammation and non-resolving pulmonary fibrosis as well as lung volumes in a sensitive and non-invasive manner. This approach and model of non-resolving lung fibrosis provides quantitative assessment of disease progression and stabilization over weeks and months, essential towards evaluation of fibrotic disease burden and antifibrotic therapy evaluation in preclinical studies.
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spelling pubmed-75275582020-10-02 Longitudinal micro-computed tomography-derived biomarkers quantify non-resolving lung fibrosis in a silicosis mouse model Dekoster, Kaat Decaesteker, Tatjana Berghen, Nathalie Van den Broucke, Sofie Jonckheere, Anne-Charlotte Wouters, Jens Krouglov, Anton Lories, Rik De Langhe, Ellen Hoet, Peter Verbeken, Erik Vanoirbeek, Jeroen Vande Velde, Greetje Sci Rep Article In spite of many compounds identified as antifibrotic in preclinical studies, pulmonary fibrosis remains a life-threatening condition for which highly effective treatment is still lacking. Towards improving the success-rate of bench-to-bedside translation, we investigated in vivo µCT-derived biomarkers to repeatedly quantify experimental silica-induced pulmonary fibrosis and assessed clinically relevant readouts up to several months after silicosis induction. Mice were oropharyngeally instilled with crystalline silica or saline and longitudinally monitored with respiratory-gated-high-resolution µCT to evaluate disease onset and progress using scan-derived biomarkers. At weeks 1, 5, 9 and 15, we assessed lung function, inflammation and fibrosis in subsets of mice in a cross-sectional manner. Silica-instillation increased the non-aerated lung volume, corresponding to onset and progression of inflammatory and fibrotic processes not resolving with time. Moreover, total lung volume progressively increased with silicosis. The volume of healthy, aerated lung first dropped then increased, corresponding to an acute inflammatory response followed by recovery into lower elevated aerated lung volume. Imaging results were confirmed by a significantly decreased Tiffeneau index, increased neutrophilic inflammation, increased IL-13, MCP-1, MIP-2 and TNF-α concentration in bronchoalveolar lavage fluid, increased collagen content and fibrotic nodules. µCT-derived biomarkers enable longitudinal evaluation of early onset inflammation and non-resolving pulmonary fibrosis as well as lung volumes in a sensitive and non-invasive manner. This approach and model of non-resolving lung fibrosis provides quantitative assessment of disease progression and stabilization over weeks and months, essential towards evaluation of fibrotic disease burden and antifibrotic therapy evaluation in preclinical studies. Nature Publishing Group UK 2020-09-30 /pmc/articles/PMC7527558/ /pubmed/32999350 http://dx.doi.org/10.1038/s41598-020-73056-6 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Dekoster, Kaat
Decaesteker, Tatjana
Berghen, Nathalie
Van den Broucke, Sofie
Jonckheere, Anne-Charlotte
Wouters, Jens
Krouglov, Anton
Lories, Rik
De Langhe, Ellen
Hoet, Peter
Verbeken, Erik
Vanoirbeek, Jeroen
Vande Velde, Greetje
Longitudinal micro-computed tomography-derived biomarkers quantify non-resolving lung fibrosis in a silicosis mouse model
title Longitudinal micro-computed tomography-derived biomarkers quantify non-resolving lung fibrosis in a silicosis mouse model
title_full Longitudinal micro-computed tomography-derived biomarkers quantify non-resolving lung fibrosis in a silicosis mouse model
title_fullStr Longitudinal micro-computed tomography-derived biomarkers quantify non-resolving lung fibrosis in a silicosis mouse model
title_full_unstemmed Longitudinal micro-computed tomography-derived biomarkers quantify non-resolving lung fibrosis in a silicosis mouse model
title_short Longitudinal micro-computed tomography-derived biomarkers quantify non-resolving lung fibrosis in a silicosis mouse model
title_sort longitudinal micro-computed tomography-derived biomarkers quantify non-resolving lung fibrosis in a silicosis mouse model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527558/
https://www.ncbi.nlm.nih.gov/pubmed/32999350
http://dx.doi.org/10.1038/s41598-020-73056-6
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