Telomerase and telomere length in pulmonary fibrosis

Tianju Liu, Matthew Ullenbruch, Yoon Young Choi, Hongfeng Yu, Lin Ding, Antoni Xaubet, Javier Pereda, Carol A. Feghali-Bostwick, Peter B. Bitterman, Craig A. Henke, Annie Pardo, Moises Selman, Sem H. Phan

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

In addition to its expression in stem cells and many cancers, telomerase activity is transiently induced inmurine bleomycin (BLM)- induced pulmonary fibrosis with increased levels of telomerase transcriptase (TERT) expression, which is essential for fibrosis. To extend these observations to human chronic fibrotic lung disease, we investigated the expression of telomerase activity in lung fibroblasts from patients with interstitial lung diseases (ILDs), including idiopathic pulmonaryfibrosis (IPF).The resultsshowedthat telomerase activity was induced in more than 66% of IPF lung fibroblast samples, in comparison with less than 29% from control samples, some of which were obtained from lung cancer resections. Less than 4%of the humanIPF lung fibroblast samples exhibited shortened telomeres, whereas less than 6% of peripheral blood leukocyte samples from patients with IPF or hypersensitivity pneumonitis demonstrated shortened telomeres. Moreover, shortened telomeres in lategeneration telomerase RNA component knockout mice did not exert a significant effect on BLM-induced pulmonary fibrosis. In contrast, TERT knockout mice exhibited deficient fibrosis that was independent of telomere length. Finally, TERT expression was up-regulated by a histone deacetylase inhibitor, while the induction of TERT in lung fibroblastswasassociatedwiththebindingofacetylatedhistoneH3K9to the TERT promoter region. These findings indicate that significant telomerase inductionwas evident in fibroblasts from fibroticmurine lungs and a majority of IPF lung samples, whereas telomere shortening was not a common finding in the human blood and lung fibroblast samples. Notably, the animal studies indicated that the pathogenesis of pulmonary fibrosis was independent of telomere length.

Original languageEnglish (US)
Pages (from-to)260-268
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume49
Issue number2
DOIs
StatePublished - Aug 2013

Bibliographical note

Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.

Keywords

  • Fibrosis
  • Telomerase
  • Telomere

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