A role for telomere length and chromosomal damage in idiopathic pulmonary fibrosis

BACKGROUND: Idiopathic pulmonary fibrosis is a fatal lung disease characterized by a progressive formation of fibroblastic foci in the interstitium. This disease is strongly associated with telomere dysfunction but the extent of telomere shortening and consequent chromosomal damage within IPF lungs...

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Autores principales: McDonough, John E., Martens, Dries S., Tanabe, Naoya, Ahangari, Farida, Verleden, Stijn E., Maes, Karen, Verleden, Geert M., Kaminski, Naftali, Hogg, James C., Nawrot, Tim S., Wuyts, Wim A., Vanaudenaerde, Bart M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038197/
https://www.ncbi.nlm.nih.gov/pubmed/29986708
http://dx.doi.org/10.1186/s12931-018-0838-4
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author McDonough, John E.
Martens, Dries S.
Tanabe, Naoya
Ahangari, Farida
Verleden, Stijn E.
Maes, Karen
Verleden, Geert M.
Kaminski, Naftali
Hogg, James C.
Nawrot, Tim S.
Wuyts, Wim A.
Vanaudenaerde, Bart M.
author_facet McDonough, John E.
Martens, Dries S.
Tanabe, Naoya
Ahangari, Farida
Verleden, Stijn E.
Maes, Karen
Verleden, Geert M.
Kaminski, Naftali
Hogg, James C.
Nawrot, Tim S.
Wuyts, Wim A.
Vanaudenaerde, Bart M.
author_sort McDonough, John E.
collection PubMed
description BACKGROUND: Idiopathic pulmonary fibrosis is a fatal lung disease characterized by a progressive formation of fibroblastic foci in the interstitium. This disease is strongly associated with telomere dysfunction but the extent of telomere shortening and consequent chromosomal damage within IPF lungs and with regional disease severity remains unknown. METHODS: Explanted IPF lungs (n = 10) were collected from transplant surgeries with six samples per lung analysed to capture the regional heterogeneity ranging from mild to severe disease. Non-used donor lungs (n = 6) were collected as “healthy” controls. Structural changes related to disease severity (microCT surface density), relative telomere length (real-time qPCR), and quantitative histology of chromosomal damage (γ-H2A.X) and extracellular matrix (elastin, total collagen, collagen 1, and collagen 3) were measured. A multivariate linear mixed-effects model controlling for subject was used to identify association of disease severity or fibrotic markers with telomere length and chromosomal damage. RESULTS: We observed shorter telomere length (p = 0.001) and increased chromosomal damage (p = 0.018) in IPF lungs compared to controls. In IPF lungs, telomere length was associated with total collagen (p < 0.001) but not with structural changes of disease severity. Chromosomal damage was positively associated with increased elastin (p = 0.006) and negatively with structural disease severity (p = 0.046). Extensive γ-H2A.X staining was also present in airway epithelial cells. CONCLUSIONS: Telomere length and chromosomal damage are involved in IPF with regional variation in telomere length and chromosomal damage associated with pathological changes in tissue structure and the extracellular matrix.
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spelling pubmed-60381972018-07-12 A role for telomere length and chromosomal damage in idiopathic pulmonary fibrosis McDonough, John E. Martens, Dries S. Tanabe, Naoya Ahangari, Farida Verleden, Stijn E. Maes, Karen Verleden, Geert M. Kaminski, Naftali Hogg, James C. Nawrot, Tim S. Wuyts, Wim A. Vanaudenaerde, Bart M. Respir Res Research BACKGROUND: Idiopathic pulmonary fibrosis is a fatal lung disease characterized by a progressive formation of fibroblastic foci in the interstitium. This disease is strongly associated with telomere dysfunction but the extent of telomere shortening and consequent chromosomal damage within IPF lungs and with regional disease severity remains unknown. METHODS: Explanted IPF lungs (n = 10) were collected from transplant surgeries with six samples per lung analysed to capture the regional heterogeneity ranging from mild to severe disease. Non-used donor lungs (n = 6) were collected as “healthy” controls. Structural changes related to disease severity (microCT surface density), relative telomere length (real-time qPCR), and quantitative histology of chromosomal damage (γ-H2A.X) and extracellular matrix (elastin, total collagen, collagen 1, and collagen 3) were measured. A multivariate linear mixed-effects model controlling for subject was used to identify association of disease severity or fibrotic markers with telomere length and chromosomal damage. RESULTS: We observed shorter telomere length (p = 0.001) and increased chromosomal damage (p = 0.018) in IPF lungs compared to controls. In IPF lungs, telomere length was associated with total collagen (p < 0.001) but not with structural changes of disease severity. Chromosomal damage was positively associated with increased elastin (p = 0.006) and negatively with structural disease severity (p = 0.046). Extensive γ-H2A.X staining was also present in airway epithelial cells. CONCLUSIONS: Telomere length and chromosomal damage are involved in IPF with regional variation in telomere length and chromosomal damage associated with pathological changes in tissue structure and the extracellular matrix. BioMed Central 2018-07-09 2018 /pmc/articles/PMC6038197/ /pubmed/29986708 http://dx.doi.org/10.1186/s12931-018-0838-4 Text en © The Author(s). 2018 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
McDonough, John E.
Martens, Dries S.
Tanabe, Naoya
Ahangari, Farida
Verleden, Stijn E.
Maes, Karen
Verleden, Geert M.
Kaminski, Naftali
Hogg, James C.
Nawrot, Tim S.
Wuyts, Wim A.
Vanaudenaerde, Bart M.
A role for telomere length and chromosomal damage in idiopathic pulmonary fibrosis
title A role for telomere length and chromosomal damage in idiopathic pulmonary fibrosis
title_full A role for telomere length and chromosomal damage in idiopathic pulmonary fibrosis
title_fullStr A role for telomere length and chromosomal damage in idiopathic pulmonary fibrosis
title_full_unstemmed A role for telomere length and chromosomal damage in idiopathic pulmonary fibrosis
title_short A role for telomere length and chromosomal damage in idiopathic pulmonary fibrosis
title_sort role for telomere length and chromosomal damage in idiopathic pulmonary fibrosis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038197/
https://www.ncbi.nlm.nih.gov/pubmed/29986708
http://dx.doi.org/10.1186/s12931-018-0838-4
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