Intermittent hypoxia mediates paraspeckle protein-1 upregulation in sleep apnea

As some evidence suggests that hypoxia might be an inducer of nuclear paraspeckle formation, we explore whether intermittent hypoxia (IH)-mediated paraspeckle protein-1 (PSPC1) overexpression might contribute to the activation of tumor growth factor (TGF)β-SMAD pathway in patients with obstructive s...

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Autores: Díaz-García, Elena, García-Tovar, Sara, Casitas, Raquel, Jaureguizar, Ana, Zamarrón, Ester, Sánchez-Sánchez, Begoña, Sastre-Perona, Ana, López-Collazo, Eduardo, García Rio, Francisco, Cubillos-Zapata, Carolina
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/716560
Acceso en línea:http://hdl.handle.net/10486/716560
https://dx.doi.org/10.3390/cancers13153888
Access Level:acceso abierto
Palabra clave:HIF1α
Intermittent hypoxia
Paraspeckle component 1
Sleep apnea
TGFβ
Medicina
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spelling Intermittent hypoxia mediates paraspeckle protein-1 upregulation in sleep apneaDíaz-García, ElenaGarcía-Tovar, SaraCasitas, RaquelJaureguizar, AnaZamarrón, EsterSánchez-Sánchez, BegoñaSastre-Perona, AnaLópez-Collazo, EduardoGarcía Rio, FranciscoCubillos-Zapata, CarolinaHIF1αIntermittent hypoxiaParaspeckle component 1Sleep apneaTGFβMedicinaAs some evidence suggests that hypoxia might be an inducer of nuclear paraspeckle formation, we explore whether intermittent hypoxia (IH)-mediated paraspeckle protein-1 (PSPC1) overexpression might contribute to the activation of tumor growth factor (TGF)β-SMAD pathway in patients with obstructive sleep apnea (OSA). This activation would promote changes in intracellular signaling that would explain the increased cancer aggressiveness reported in these patients. Here, we show that patients with OSA exhibit elevated PSPC1 levels both in plasma and in monocytes. Our data suggest that PSPC1 is ultimately delivered to the plasma through its cleavage from OSA monocytes by matrix metalloproteinase-2 (MMP2). In addition, IH promotes PSPC1, TGFβ, and MMP2 expression in monocytes through the hypoxia-inducible factor. Lastly, both PSPC1 and TGFβ induce increased expression of genes that drive the epithelial-to-mesenchymal transition. Our study details the mechanism by which hypoxemia upmodulates the extracellular release of PSPC1 by means of MMP2, such that plasma PSPC1 together with TGFβ activation signaling further promotes tumor metastasis and supports cancer aggressiveness in patients with OSAThis research was funded by Health Research Fund (Fondo de Investigación Sanitaria, FIS) and ERDF Funds (Fondos FEDER), grant numbers PI16/00201 and PI19/01612 (F.G-R.), PI19/01363 (C.C-Z.) and PIE15/00065 (E.L-C.)MDPIDepartamento de MedicinaFacultad de Medicina20212021-08-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/716560https://dx.doi.org/10.3390/cancers13153888reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7165602026-06-23T12:46:27Z
dc.title.none.fl_str_mv Intermittent hypoxia mediates paraspeckle protein-1 upregulation in sleep apnea
title Intermittent hypoxia mediates paraspeckle protein-1 upregulation in sleep apnea
spellingShingle Intermittent hypoxia mediates paraspeckle protein-1 upregulation in sleep apnea
Díaz-García, Elena
HIF1α
Intermittent hypoxia
Paraspeckle component 1
Sleep apnea
TGFβ
Medicina
title_short Intermittent hypoxia mediates paraspeckle protein-1 upregulation in sleep apnea
title_full Intermittent hypoxia mediates paraspeckle protein-1 upregulation in sleep apnea
title_fullStr Intermittent hypoxia mediates paraspeckle protein-1 upregulation in sleep apnea
title_full_unstemmed Intermittent hypoxia mediates paraspeckle protein-1 upregulation in sleep apnea
title_sort Intermittent hypoxia mediates paraspeckle protein-1 upregulation in sleep apnea
dc.creator.none.fl_str_mv Díaz-García, Elena
García-Tovar, Sara
Casitas, Raquel
Jaureguizar, Ana
Zamarrón, Ester
Sánchez-Sánchez, Begoña
Sastre-Perona, Ana
López-Collazo, Eduardo
García Rio, Francisco
Cubillos-Zapata, Carolina
author Díaz-García, Elena
author_facet Díaz-García, Elena
García-Tovar, Sara
Casitas, Raquel
Jaureguizar, Ana
Zamarrón, Ester
Sánchez-Sánchez, Begoña
Sastre-Perona, Ana
López-Collazo, Eduardo
García Rio, Francisco
Cubillos-Zapata, Carolina
author_role author
author2 García-Tovar, Sara
Casitas, Raquel
Jaureguizar, Ana
Zamarrón, Ester
Sánchez-Sánchez, Begoña
Sastre-Perona, Ana
López-Collazo, Eduardo
García Rio, Francisco
Cubillos-Zapata, Carolina
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Medicina
Facultad de Medicina
dc.subject.none.fl_str_mv HIF1α
Intermittent hypoxia
Paraspeckle component 1
Sleep apnea
TGFβ
Medicina
topic HIF1α
Intermittent hypoxia
Paraspeckle component 1
Sleep apnea
TGFβ
Medicina
description As some evidence suggests that hypoxia might be an inducer of nuclear paraspeckle formation, we explore whether intermittent hypoxia (IH)-mediated paraspeckle protein-1 (PSPC1) overexpression might contribute to the activation of tumor growth factor (TGF)β-SMAD pathway in patients with obstructive sleep apnea (OSA). This activation would promote changes in intracellular signaling that would explain the increased cancer aggressiveness reported in these patients. Here, we show that patients with OSA exhibit elevated PSPC1 levels both in plasma and in monocytes. Our data suggest that PSPC1 is ultimately delivered to the plasma through its cleavage from OSA monocytes by matrix metalloproteinase-2 (MMP2). In addition, IH promotes PSPC1, TGFβ, and MMP2 expression in monocytes through the hypoxia-inducible factor. Lastly, both PSPC1 and TGFβ induce increased expression of genes that drive the epithelial-to-mesenchymal transition. Our study details the mechanism by which hypoxemia upmodulates the extracellular release of PSPC1 by means of MMP2, such that plasma PSPC1 together with TGFβ activation signaling further promotes tumor metastasis and supports cancer aggressiveness in patients with OSA
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-08-01
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
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/10486/716560
https://dx.doi.org/10.3390/cancers13153888
url http://hdl.handle.net/10486/716560
https://dx.doi.org/10.3390/cancers13153888
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
Attribution 4.0 International
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
Attribution 4.0 International
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 MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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