UBC Faculty Research and Publications

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

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 

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