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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.; et al.

Abstract

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.

Item Metadata

Title
A role for telomere length and chromosomal damage in idiopathic pulmonary fibrosis
Creator
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.
Contributor
Centre for Heart Lung Innovation
Publisher
BioMed Central
Date Issued
2018-07-09
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.
Subject
IPF; Telomere length; Gamma-H2AX; Fibrosis; Collagen 1; Elastin; microCT
Genre
Article
Type
Text
Language
eng
Date Available
2018-07-09
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0368853
URI
http://hdl.handle.net/2429/66448
Affiliation
Other UBC; Non UBC
Citation
Respiratory Research. 2018 Jul 09;19(1):132
Publisher DOI
10.1186/s12931-018-0838-4
Peer Review Status
Reviewed
Scholarly Level
Faculty
Copyright Holder
The Author(s).
Rights URI
http://creativecommons.org/licenses/by/4.0/
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Attribution 4.0 International (CC BY 4.0)