Lung fibroblasts from idiopathic pulmonary fibrosis patients harbor short and unstable telomeres leading to chromosomal instability

Date

2022

Authors

M'kacher, R.
Jaillet, M.
Colicchio, B.
Vasarmidi, E.
Mailleux, A.
Dieterlen, A.
Kannengiesser, C.
Borie, C.
Oudrhiri, N.
Junker, S.

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Journal article

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Biomedicines, 2022; 10(2, article no. 310):1-13

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Abstract

Idiopathic pulmonary fibrosis (IPF) is associated with several hallmarks of aging including telomere shortening, which can result from germline mutations in telomere related genes (TRGs). Here, we assessed the length and stability of telomeres as well as the integrity of chromosomes in primary lung fibroblasts from 13 IPF patients (including seven patients with pathogenic variants in TRGs) and seven controls. Automatized high-throughput detection of telomeric FISH signals highlighted lower signal intensity in lung fibroblasts from IPF patients, suggesting a telomere length defect in these cells. The increased detection of telomere loss and terminal deletion in IPF cells, particularly in TRG-mutated cells (IPF-TRG), supports the notion that these cells have unstable telomeres. Furthermore, fibroblasts from IPF patients with TRGs mutations exhibited dicentric chromosomes and anaphase bridges. Collectively, our study indicates that fibroblasts from IPF patients exhibit telomere and chromosome instability that likely contribute to the physiopathology.

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Copyright 2022 The author(s). This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (https://creativecommons.org/licenses/by/4.0/)

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