Therapeutic effects of telomerase in mice with pulmonary fibrosis induced by damage to the lungs and short telomeres.

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...

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Autores: Povedano, Juan Manuel, Martinez, Paula, Serrano, Rosa, Tejera, Águeda, Gómez López, Gonzalo, Bobadilla, Maria, Flores, Juana Maria, Bosch, Fàtima, Blasco, María A.
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universidad Francisco de Vitoria
Repositorio:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
Idioma:inglés
OAI Identifier:oai:ddfv.ufv.es:10641/3541
Acceso en línea:https://hdl.handle.net/10641/3541
Access Level:acceso abierto
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spelling Therapeutic effects of telomerase in mice with pulmonary fibrosis induced by damage to the lungs and short telomeres.Povedano, Juan ManuelMartinez, PaulaSerrano, RosaTejera, ÁguedaGómez López, GonzaloBobadilla, MariaFlores, Juana MariaBosch, FàtimaBlasco, María A.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.20182018-01-0120182018-01-01journal articlehttp://purl.org/coar/resource_type/c_6501AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10641/3541reponame:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoriainstname:Universidad Francisco de VitoriaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución-NoComercial-SinDerivadas 3.0 Españahttp://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:ddfv.ufv.es:10641/35412026-06-11T12:44:57Z
dc.title.none.fl_str_mv Therapeutic effects of telomerase in mice with pulmonary fibrosis induced by damage to the lungs and short telomeres.
title Therapeutic effects of telomerase in mice with pulmonary fibrosis induced by damage to the lungs and short telomeres.
spellingShingle Therapeutic effects of telomerase in mice with pulmonary fibrosis induced by damage to the lungs and short telomeres.
Povedano, Juan Manuel
title_short Therapeutic effects of telomerase in mice with pulmonary fibrosis induced by damage to the lungs and short telomeres.
title_full Therapeutic effects of telomerase in mice with pulmonary fibrosis induced by damage to the lungs and short telomeres.
title_fullStr Therapeutic effects of telomerase in mice with pulmonary fibrosis induced by damage to the lungs and short telomeres.
title_full_unstemmed Therapeutic effects of telomerase in mice with pulmonary fibrosis induced by damage to the lungs and short telomeres.
title_sort Therapeutic effects of telomerase in mice with pulmonary fibrosis induced by damage to the lungs and short telomeres.
dc.creator.none.fl_str_mv Povedano, Juan Manuel
Martinez, Paula
Serrano, Rosa
Tejera, Águeda
Gómez López, Gonzalo
Bobadilla, Maria
Flores, Juana Maria
Bosch, Fàtima
Blasco, María A.
author Povedano, Juan Manuel
author_facet Povedano, Juan Manuel
Martinez, Paula
Serrano, Rosa
Tejera, Águeda
Gómez López, Gonzalo
Bobadilla, Maria
Flores, Juana Maria
Bosch, Fàtima
Blasco, María A.
author_role author
author2 Martinez, Paula
Serrano, Rosa
Tejera, Águeda
Gómez López, Gonzalo
Bobadilla, Maria
Flores, Juana Maria
Bosch, Fàtima
Blasco, María A.
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
description 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.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-01-01
2018
2018-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10641/3541
url https://hdl.handle.net/10641/3541
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial-SinDerivadas 3.0 España
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial-SinDerivadas 3.0 España
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
instname:Universidad Francisco de Vitoria
instname_str Universidad Francisco de Vitoria
reponame_str DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
collection DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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