2026-06-14T03:29:07Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/65872024-11-29T19:48:06Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Povedano Selfa, Juan Manuel
author
Martinez Rodriguez , Paula
author
Serrano Ruiz, Rosa
author
Tejera, Agueda
author
Gomez Lopez, Gonzalo
author
Bobadilla, Maria
author
Flores, Juana Maria
author
Bosch, Fátima
author
Blasco MA, Maria A
funder
Ministerio de Economía y Competitividad (España)
2018-11-14T11:38:50Z
2018-11-14T11:38:50Z
2018-01-30
Elife. 2018; 30 : 7.
10.7554/eLife.31299
2050-084X
2050-084X
eLife
29378675
http://hdl.handle.net/20.500.12105/6587
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.
eng
AAV9
Chromosomes
Gene therapy
Genes
Mouse
Pulmonary fibrosis
Telomerase
Telomeres
Therapeutic effects of telomerase in mice with pulmonary fibrosis induced by damage to the lungs and short telomeres
journal article
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Therapeuticeffectsoftelomerase_2018.pdf
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Therapeuticeffectsoftelomerase_2018-figures-v2.pdf
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Therapeuticeffectsoftelomerase_2018.pdf.txt
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