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dc.contributor.authorPovedano Selfa, Juan Manuel 
dc.contributor.authorMartinez Rodriguez , Paula 
dc.contributor.authorSerrano Ruiz, Rosa 
dc.contributor.authorTejera, Agueda 
dc.contributor.authorGomez Lopez, Gonzalo 
dc.contributor.authorBobadilla, Maria
dc.contributor.authorFlores, Juana Maria
dc.contributor.authorBosch, Fátima
dc.contributor.authorBlasco MA, Maria A 
dc.date.accessioned2018-11-14T11:38:50Z
dc.date.available2018-11-14T11:38:50Z
dc.date.issued2018-01-30
dc.identifier.citationElife. 2018; 30 : 7.es_ES
dc.identifier.issn2050-084Xes_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6587
dc.description.abstractPulmonary 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.es_ES
dc.description.sponsorshipWe are indebted to D Megias for microscopy analysis, to J Mun˜ oz and F Garcı´a for hydroxiproline analysis as well as to CNIO Histopathological Unit. The research was funded by project SAF2013- 45111-R of Societal Changes Programme of the Spanish Ministry of Economics and Competitiveness (MINECO) co-financed through the European Fund of Regional Development (FEDER), Fundacio´n Botı´n and Banco Santander (Santander Universities Global Division) and Roche Extending the Innova- tion Network Program (EIN) Academia Partnering Programme.es_ES
dc.language.isoenges_ES
dc.publishereLife Sciences Publicationses_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectAAV9es_ES
dc.subjectchromosomeses_ES
dc.subjectgene therapyes_ES
dc.subjectgeneses_ES
dc.subjectmousees_ES
dc.subjectpulmonary fibrosises_ES
dc.subjecttelomerasees_ES
dc.subjecttelomereses_ES
dc.titleTherapeutic effects of telomerase in mice with pulmonary fibrosis induced by damage to the lungs and short telomereses_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID29378675es_ES
dc.format.volume7es_ES
dc.identifier.doi10.7554/eLife.31299es_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.description.peerreviewed
dc.identifier.e-issn2050-084Xes_ES
dc.relation.publisherversionhttps://doi.org/10.7554/eLife.31299.es_ES
dc.identifier.journaleLifees_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Telómeros y Telomerasaes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2013-45111-Res_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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