From U Michigan: Telomerase and telomere length in pulmonary fibrosis

http://www.ncbi.nlm.nih.gov/pubmed/23526226

Am J Respir Cell Mol Biol. 2013 Aug;49(2):260-8. doi: 10.1165/rcmb.2012-0514OC.

Telomerase and telomere length in pulmonary fibrosis.

Liu T, Ullenbruch M, Young Choi Y, Yu H, Ding L, Xaubet A, Pereda J, Feghali-Bostwick CA, Bitterman PB, Henke CA, Pardo A, Selman M, Phan SH.

Source

1 Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan.

Abstract

In addition to its expression in stem cells and many cancers, telomerase activity is transiently induced in murine 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 lungdiseases (ILDs), including idiopathic pulmonary fibrosis (IPF). The results showed that telomerase activity was induced in more than 66% of IPF lungfibroblast samples, in comparison with less than 29% from control samples, some of which were obtained from lung cancer resections. Less than 4% of the human IPF 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 late-generation 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 ofTERT in lung fibroblasts was associated with the binding of acetylated histone H3K9 to the TERT promoter region. These findings indicate that significant telomerase induction was evident in fibroblasts from fibrotic murine 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.