Accelerated aging induced by deficiency of Zmpste24 protects old mice to develop bleomycin-induced pulmonary fibrosis

Idiopathic pulmonary fibrosis is a devastating aging-associated disease of unknown etiology. Despite that aging is a major risk factor, the mechanisms linking aging with this disease are uncertain, and experimental models to explore them in lung fibrosis are scanty. We examined the fibrotic response...

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Autor: VILMA ARACELI MALDONADO LAGUNAS
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:México
Institución:Instituto Nacional de Medicina Genómica
Repositorio:Repositorio del Instituto Nacional de Medicina Genómica
Idioma:inglés
OAI Identifier:oai:repositorio.inmegen.gob.mx:274
Acceso en línea:http://repositorio.inmegen.gob.mx/record/274
Access Level:acceso abierto
Palabra clave:info:eu-repo/classification/cti/3
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repository_id_str
spelling Accelerated aging induced by deficiency of Zmpste24 protects old mice to develop bleomycin-induced pulmonary fibrosisVILMA ARACELI MALDONADO LAGUNASinfo:eu-repo/classification/cti/3 Idiopathic pulmonary fibrosis is a devastating aging-associated disease of unknown etiology. Despite that aging is a major risk factor, the mechanisms linking aging with this disease are uncertain, and experimental models to explore them in lung fibrosis are scanty. We examined the fibrotic response to bleomycin-induced lung injury in Zmpste24-deficient mice, which exhibit nuclear lamina defects developing accelerated aging. We found that young WT and Zmpste24(-/-) mice developed a similar fibrotic response to bleomycin. Unexpectedly, while old WT mice developed severe lung fibrosis, accelerated aged Zmpste24-/- mice were protected showing scant lung damage. To investigate possible mechanisms associated with this resistance to fibrosis, we compared the transcriptome signature of the lungs and found that Zmpste24(-/-) mice showed downregulation of several core and associated matrisome genes compared with WT mice. Interestingly, some microRNAs that target extracellular matrix molecules such as miR23a, miR27a, miR29a, miR29b-1, miR145a, and miR491 were dysregulated resulting in downregulation of profibrotic pathways such as TGF-beta/SMAD3/NF-kappaB and Wnt3a/beta-catenin signaling axis. These results indicate that the absence of Zmpste24 in aging mice results in impaired lung fibrotic response after injury, which is likely associated to the dysregulation of fibrosis-related miRNAs. Aging-US2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://repositorio.inmegen.gob.mx/record/274reponame:Repositorio del Instituto Nacional de Medicina Genómicainstname:Instituto Nacional de Medicina Genómicainstacron:INMIGENenginfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0oai:repositorio.inmegen.gob.mx:2742024-08-28T06:40:10Z
dc.title.none.fl_str_mv Accelerated aging induced by deficiency of Zmpste24 protects old mice to develop bleomycin-induced pulmonary fibrosis
title Accelerated aging induced by deficiency of Zmpste24 protects old mice to develop bleomycin-induced pulmonary fibrosis
spellingShingle Accelerated aging induced by deficiency of Zmpste24 protects old mice to develop bleomycin-induced pulmonary fibrosis
VILMA ARACELI MALDONADO LAGUNAS
info:eu-repo/classification/cti/3
title_short Accelerated aging induced by deficiency of Zmpste24 protects old mice to develop bleomycin-induced pulmonary fibrosis
title_full Accelerated aging induced by deficiency of Zmpste24 protects old mice to develop bleomycin-induced pulmonary fibrosis
title_fullStr Accelerated aging induced by deficiency of Zmpste24 protects old mice to develop bleomycin-induced pulmonary fibrosis
title_full_unstemmed Accelerated aging induced by deficiency of Zmpste24 protects old mice to develop bleomycin-induced pulmonary fibrosis
title_sort Accelerated aging induced by deficiency of Zmpste24 protects old mice to develop bleomycin-induced pulmonary fibrosis
dc.creator.none.fl_str_mv VILMA ARACELI MALDONADO LAGUNAS
author VILMA ARACELI MALDONADO LAGUNAS
author_facet VILMA ARACELI MALDONADO LAGUNAS
author_role author
dc.subject.none.fl_str_mv info:eu-repo/classification/cti/3
topic info:eu-repo/classification/cti/3
description Idiopathic pulmonary fibrosis is a devastating aging-associated disease of unknown etiology. Despite that aging is a major risk factor, the mechanisms linking aging with this disease are uncertain, and experimental models to explore them in lung fibrosis are scanty. We examined the fibrotic response to bleomycin-induced lung injury in Zmpste24-deficient mice, which exhibit nuclear lamina defects developing accelerated aging. We found that young WT and Zmpste24(-/-) mice developed a similar fibrotic response to bleomycin. Unexpectedly, while old WT mice developed severe lung fibrosis, accelerated aged Zmpste24-/- mice were protected showing scant lung damage. To investigate possible mechanisms associated with this resistance to fibrosis, we compared the transcriptome signature of the lungs and found that Zmpste24(-/-) mice showed downregulation of several core and associated matrisome genes compared with WT mice. Interestingly, some microRNAs that target extracellular matrix molecules such as miR23a, miR27a, miR29a, miR29b-1, miR145a, and miR491 were dysregulated resulting in downregulation of profibrotic pathways such as TGF-beta/SMAD3/NF-kappaB and Wnt3a/beta-catenin signaling axis. These results indicate that the absence of Zmpste24 in aging mice results in impaired lung fibrotic response after injury, which is likely associated to the dysregulation of fibrosis-related miRNAs.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://repositorio.inmegen.gob.mx/record/274
url http://repositorio.inmegen.gob.mx/record/274
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0
dc.format.none.fl_str_mv
dc.publisher.none.fl_str_mv Aging-US
publisher.none.fl_str_mv Aging-US
dc.source.none.fl_str_mv reponame:Repositorio del Instituto Nacional de Medicina Genómica
instname:Instituto Nacional de Medicina Genómica
instacron:INMIGEN
instname_str Instituto Nacional de Medicina Genómica
instacron_str INMIGEN
institution INMIGEN
reponame_str Repositorio del Instituto Nacional de Medicina Genómica
collection Repositorio del Instituto Nacional de Medicina Genómica
repository.name.fl_str_mv
repository.mail.fl_str_mv
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