From organ to cell: Multi-level telomere length assessment in patients with idiopathic pulmonary fibrosis.
<h4>Rationale</h4>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 telomer...
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| Format: | Article |
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Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0226785&type=printable |
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| author | Aernoud A van Batenburg Karin M Kazemier Matthijs F M van Oosterhout Joanne J van der Vis Hendrik W van Es Jan C Grutters Roel Goldschmeding Coline H M van Moorsel |
| author_facet | Aernoud A van Batenburg Karin M Kazemier Matthijs F M van Oosterhout Joanne J van der Vis Hendrik W van Es Jan C Grutters Roel Goldschmeding Coline H M van Moorsel |
| author_sort | Aernoud A van Batenburg |
| collection | DOAJ |
| description | <h4>Rationale</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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. |
| format | Article |
| id | doaj-art-4ae107799ebb4bf0aae8e6d79b04d1a5 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-4ae107799ebb4bf0aae8e6d79b04d1a52025-08-20T02:17:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01151e022678510.1371/journal.pone.0226785From organ to cell: Multi-level telomere length assessment in patients with idiopathic pulmonary fibrosis.Aernoud A van BatenburgKarin M KazemierMatthijs F M van OosterhoutJoanne J van der VisHendrik W van EsJan C GruttersRoel GoldschmedingColine H M van Moorsel<h4>Rationale</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0226785&type=printable |
| spellingShingle | Aernoud A van Batenburg Karin M Kazemier Matthijs F M van Oosterhout Joanne J van der Vis Hendrik W van Es Jan C Grutters Roel Goldschmeding Coline H M van Moorsel From organ to cell: Multi-level telomere length assessment in patients with idiopathic pulmonary fibrosis. PLoS ONE |
| title | From organ to cell: Multi-level telomere length assessment in patients with idiopathic pulmonary fibrosis. |
| title_full | From organ to cell: Multi-level telomere length assessment in patients with idiopathic pulmonary fibrosis. |
| title_fullStr | From organ to cell: Multi-level telomere length assessment in patients with idiopathic pulmonary fibrosis. |
| title_full_unstemmed | From organ to cell: Multi-level telomere length assessment in patients with idiopathic pulmonary fibrosis. |
| title_short | From organ to cell: Multi-level telomere length assessment in patients with idiopathic pulmonary fibrosis. |
| title_sort | from organ to cell multi level telomere length assessment in patients with idiopathic pulmonary fibrosis |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0226785&type=printable |
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