Therapeutic effects of telomerase in mice with pulmonary fibrosis induced by damage to the lungs and short telomeres
- Spanish National Cancer Centre (CNIO), Spain
- F. Hoffmann-La Roche Ltd, Switzerland
- Complutense University of Madrid, Spain
- Autonomous University of Barcelona, Spain
Abstract
Pulmonary fibrosis is a fatal lung disease characterized by fibrotic foci and inflammatory infiltrates. Short telomeres can impair tissue regeneration and are found both in hereditary and sporadic cases. We show here that telomerase expression using AAV9 vectors shows therapeutic effects in a mouse model of pulmonary fibrosis owing to a low-dose bleomycin insult and short telomeres. AAV9 preferentially targets regenerative alveolar type II cells (ATII). AAV9-Tert-treated mice show improved lung function and lower inflammation and fibrosis at 1-3 weeks after viral treatment, and improvement or disappearance of the fibrosis at 8 weeks after treatment. AAV9-Tert treatment leads to longer telomeres and increased proliferation of ATII cells, as well as lower DNA damage, apoptosis, and senescence. Transcriptome analysis of ATII cells confirms downregulation of fibrosis and inflammation pathways. We provide a proof-of-principle that telomerase activation may represent an effective treatment for pulmonary fibrosis provoked or associated with short telomeres.
Data availability
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Therapeutic effects of telomerase in mice with pulmonary fibrosis induced by damage to the lungs and short telomeresPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE93869).
Article and author information
Author details
Funding
Ministerio de Economía y Competitividad (SAF2013-45111-R)
- Paula Martinez
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Kathleen Collins, University of California, Berkeley, United States
Ethics
Animal experimentation: Animal procedures were approved by the CNIO-ISCIII Ethics Committee for Research and Animal Welfare (CEIyBA) and conducted in accordance to the recommendations of the Federation of European Laboratory Animal Science Associations (FELASA).
Version history
- Received: August 16, 2017
- Accepted: January 23, 2018
- Accepted Manuscript published: January 30, 2018 (version 1)
- Version of Record published: February 19, 2018 (version 2)
Copyright
© 2018, Povedano et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Therapeutic effects of telomerase in mice with pulmonary fibrosis induced by damage to the lungs and short telomeres
eLife 7:e31299.
https://doi.org/10.7554/eLife.31299
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