mTert induction in p21-positive cells counteracts capillary rarefaction and pulmonary emphysema.

Lung diseases develop when telomeres shorten beyond a critical point. We constructed a mouse model in which the catalytic subunit of telomerase (mTert), or its catalytically inactive form (mTertCI), is expressed from the p21Cdkn1a locus. Expression of either TERT or TERTCI reduces global p21 levels...

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Detalles Bibliográficos
Autores: Lipskaia, Larissa, Breau, Marielle, Cayrou, Christelle, Churikov, Dmitri, Braud, Laura, Jacquet, Juliette, Born, Emmanuelle, Fouillade, Charles, Curras-Alonso, Sandra, Bauwens, Serge, Jourquin, Frederic, Fiore, Frederic, Castellano, Rémy, Josselin, Emmanuelle, Sánchez-Ferrer, Carlota, Giovinazzo, Giovanna, Lachaud, Christophe, Gilson, Eric, Flores, Ignacio, Londono-Vallejo, Arturo, Adnot, Serge, Géli, Vincent
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/20039
Acceso en línea:http://hdl.handle.net/20.500.12105/20039
Access Level:acceso abierto
Palabra clave:Pulmonary Emphysema
Microvascular Rarefaction
Emphysema
Telomerase
Mice
Animals
Telomere Shortening
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spelling mTert induction in p21-positive cells counteracts capillary rarefaction and pulmonary emphysema.Lipskaia, LarissaBreau, MarielleCayrou, ChristelleChurikov, DmitriBraud, LauraJacquet, JulietteBorn, EmmanuelleFouillade, CharlesCurras-Alonso, SandraBauwens, SergeJourquin, FredericFiore, FredericCastellano, RémyJosselin, EmmanuelleSánchez-Ferrer, CarlotaGiovinazzo, GiovannaLachaud, ChristopheGilson, EricFlores, IgnacioLondono-Vallejo, ArturoAdnot, SergeGéli, VincentPulmonary EmphysemaMicrovascular RarefactionEmphysemaTelomeraseMiceAnimalsTelomere ShorteningLung diseases develop when telomeres shorten beyond a critical point. We constructed a mouse model in which the catalytic subunit of telomerase (mTert), or its catalytically inactive form (mTertCI), is expressed from the p21Cdkn1a locus. Expression of either TERT or TERTCI reduces global p21 levels in the lungs of aged mice, highlighting TERT non-canonical function. However, only TERT reduces accumulation of very short telomeres, oxidative damage, endothelial cell (ECs) senescence and senile emphysema in aged mice. Single-cell analysis of the lung reveals that p21 (and hence TERT) is expressed mainly in the capillary ECs. We report that a fraction of capillary ECs marked by CD34 and endowed with proliferative capacity declines drastically with age, and this is counteracted by TERT but not TERTCI. Consistently, only TERT counteracts decline of capillary density. Natural aging effects are confirmed using the experimental model of emphysema induced by VEGFR2 inhibition and chronic hypoxia. We conclude that catalytically active TERT prevents exhaustion of the putative CD34 + EC progenitors with age, thus protecting against capillary vessel loss and pulmonary emphysema.WileyMinisterio de Ciencia e Innovación (España)Comunidad de Madrid (España)Unión Europea. Comisión Europea. H202020242024-07-0420242024-03-0120242024-03-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/20039reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/200392026-06-12T12:43:37Z
dc.title.none.fl_str_mv mTert induction in p21-positive cells counteracts capillary rarefaction and pulmonary emphysema.
title mTert induction in p21-positive cells counteracts capillary rarefaction and pulmonary emphysema.
spellingShingle mTert induction in p21-positive cells counteracts capillary rarefaction and pulmonary emphysema.
Lipskaia, Larissa
Pulmonary Emphysema
Microvascular Rarefaction
Emphysema
Telomerase
Mice
Animals
Telomere Shortening
title_short mTert induction in p21-positive cells counteracts capillary rarefaction and pulmonary emphysema.
title_full mTert induction in p21-positive cells counteracts capillary rarefaction and pulmonary emphysema.
title_fullStr mTert induction in p21-positive cells counteracts capillary rarefaction and pulmonary emphysema.
title_full_unstemmed mTert induction in p21-positive cells counteracts capillary rarefaction and pulmonary emphysema.
title_sort mTert induction in p21-positive cells counteracts capillary rarefaction and pulmonary emphysema.
dc.creator.none.fl_str_mv Lipskaia, Larissa
Breau, Marielle
Cayrou, Christelle
Churikov, Dmitri
Braud, Laura
Jacquet, Juliette
Born, Emmanuelle
Fouillade, Charles
Curras-Alonso, Sandra
Bauwens, Serge
Jourquin, Frederic
Fiore, Frederic
Castellano, Rémy
Josselin, Emmanuelle
Sánchez-Ferrer, Carlota
Giovinazzo, Giovanna
Lachaud, Christophe
Gilson, Eric
Flores, Ignacio
Londono-Vallejo, Arturo
Adnot, Serge
Géli, Vincent
author Lipskaia, Larissa
author_facet Lipskaia, Larissa
Breau, Marielle
Cayrou, Christelle
Churikov, Dmitri
Braud, Laura
Jacquet, Juliette
Born, Emmanuelle
Fouillade, Charles
Curras-Alonso, Sandra
Bauwens, Serge
Jourquin, Frederic
Fiore, Frederic
Castellano, Rémy
Josselin, Emmanuelle
Sánchez-Ferrer, Carlota
Giovinazzo, Giovanna
Lachaud, Christophe
Gilson, Eric
Flores, Ignacio
Londono-Vallejo, Arturo
Adnot, Serge
Géli, Vincent
author_role author
author2 Breau, Marielle
Cayrou, Christelle
Churikov, Dmitri
Braud, Laura
Jacquet, Juliette
Born, Emmanuelle
Fouillade, Charles
Curras-Alonso, Sandra
Bauwens, Serge
Jourquin, Frederic
Fiore, Frederic
Castellano, Rémy
Josselin, Emmanuelle
Sánchez-Ferrer, Carlota
Giovinazzo, Giovanna
Lachaud, Christophe
Gilson, Eric
Flores, Ignacio
Londono-Vallejo, Arturo
Adnot, Serge
Géli, Vincent
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Comunidad de Madrid (España)
Unión Europea. Comisión Europea. H2020
dc.subject.none.fl_str_mv Pulmonary Emphysema
Microvascular Rarefaction
Emphysema
Telomerase
Mice
Animals
Telomere Shortening
topic Pulmonary Emphysema
Microvascular Rarefaction
Emphysema
Telomerase
Mice
Animals
Telomere Shortening
description Lung diseases develop when telomeres shorten beyond a critical point. We constructed a mouse model in which the catalytic subunit of telomerase (mTert), or its catalytically inactive form (mTertCI), is expressed from the p21Cdkn1a locus. Expression of either TERT or TERTCI reduces global p21 levels in the lungs of aged mice, highlighting TERT non-canonical function. However, only TERT reduces accumulation of very short telomeres, oxidative damage, endothelial cell (ECs) senescence and senile emphysema in aged mice. Single-cell analysis of the lung reveals that p21 (and hence TERT) is expressed mainly in the capillary ECs. We report that a fraction of capillary ECs marked by CD34 and endowed with proliferative capacity declines drastically with age, and this is counteracted by TERT but not TERTCI. Consistently, only TERT counteracts decline of capillary density. Natural aging effects are confirmed using the experimental model of emphysema induced by VEGFR2 inhibition and chronic hypoxia. We conclude that catalytically active TERT prevents exhaustion of the putative CD34 + EC progenitors with age, thus protecting against capillary vessel loss and pulmonary emphysema.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-07-04
2024
2024-03-01
2024
2024-03-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/20039
url http://hdl.handle.net/20.500.12105/20039
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 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
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 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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