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Respir Res. 2018 Jul 9;19(1):132. doi: 10.1186/s12931-018-0838-4.

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

Author information

1
Laboratory of Respiratory Diseases, Department of Chronic Diseases, Metabolism, and Ageing, KU Leuven, Herestraat 49, O&N I, box 706, B-3000, Leuven, Belgium. john.mcdonough@kuleuven.be.
2
Centre for Environmental Sciences, Hasselt University, Hasselt, Belgium.
3
University of British Columbia, Centre for Heart Lung Innovation, Vancouver, BC, Canada.
4
Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University, New Haven, CT, USA.
5
Laboratory of Respiratory Diseases, Department of Chronic Diseases, Metabolism, and Ageing, KU Leuven, Herestraat 49, O&N I, box 706, B-3000, Leuven, Belgium.

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.

KEYWORDS:

Collagen 1; Elastin; Fibrosis; Gamma-H2AX; IPF; Telomere length; microCT

PMID:
29986708
PMCID:
PMC6038197
DOI:
10.1186/s12931-018-0838-4
[Indexed for MEDLINE]
Free PMC Article

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