From organ to cell: Multi-level telomere length assessment in patients with idiopathic pulmonary fibrosis
Autoři:
Aernoud A. van Batenburg aff001; Karin M. Kazemier aff002; Matthijs F. M. van Oosterhout aff004; Joanne J. van der Vis aff001; Hendrik W. van Es aff006; Jan C. Grutters aff001; Roel Goldschmeding aff008; Coline H. M. van Moorsel aff001
Působiště autorů:
Department of Pulmonology, St Antonius ILD Center of Excellence, St Antonius Hospital, Nieuwegein, the Netherlands
aff001; Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands
aff002; Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, the Netherlands
aff003; Pathology–DNA, Department of Pathology, St Antonius ILD Center of Excellence St Antonius Hospital, Nieuwegein, The Netherlands
aff004; Department of Clinical Chemistry, St Antonius ILD Center of Excellence, St Antonius Hospital, Nieuwegein, the Netherlands
aff005; Department of Radiology, St Antonius ILD Center of Excellence, St Antonius Hospital, Nieuwegein, the Netherlands
aff006; Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, the Netherlands
aff007; Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands
aff008
Vyšlo v časopise:
PLoS ONE 15(1)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0226785
Souhrn
Rationale
A subset of patients with idiopathic pulmonary fibrosis (IPF) contains short leukocyte telomeres or telomere related mutations. We previously showed that alveolar type 2 cells have short telomeres in fibrotic lesions. Our objectives were to better understand how telomere shortening associates with fibrosis in IPF lung and identify a subset of patients with telomere-related disease.
Methods
Average telomere length was determined in multiple organs, basal and apical lung, and diagnostic and end-stage fibrotic lung biopsies. Alveolar type 2 cells telomere length was determined in different areas of IPF lungs.
Results
In IPF but not in controls, telomere length in lung was shorter than in other organs, providing rationale to focus on telomere length in lung. Telomere length did not correlate with age and no difference in telomere length was found between diagnostic and explant lung or between basal and apical lung, irrespective of the presence of a radiological apicobasal gradient or fibrosis. Fifteen out of 28 IPF patients had average lung telomere length in the range of patients with a telomerase (TERT) mutation, and formed the IPFshort group. Only in this IPFshort and TERT group telomeres of alveolar type 2 cells were extremely short in fibrotic areas. Additionally, whole exome sequencing of IPF patients revealed two genetic variations in RTEL1 and one in PARN in the IPFshort group.
Conclusions
Average lung tissue telomere shortening does not associated with fibrotic patterns in IPF, however, approximately half of IPF patients show excessive lung telomere shortening that is associated with pulmonary fibrosis driven by telomere attrition.
Klíčová slova:
Biopsy – Diagnostic medicine – Fibrosis – Fluorescent in situ hybridization – Lungs – Pulmonary fibrosis – Telomere length – Telomeres
Zdroje
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