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...
| Autores: | ; ; ; ; ; ; ; ; ; |
|---|---|
| Tipo de documento: | Artículo |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Universidad Autónoma de Madrid |
| Repositorio: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Lenguaje: | 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 |
| Nivel de acceso: | Acceso abierto |
| Palabra clave: | HIF1α Intermittent hypoxia Paraspeckle component 1 Sleep apnea TGFβ Medicina |
| _version_ | 1878733864460877824 |
|---|---|
| author | Díaz-García, Elena |
| 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 |
| author_browse | Casitas, Raquel Cubillos-Zapata, Carolina Díaz-García, Elena García Rio, Francisco García-Tovar, Sara Jaureguizar, Ana López-Collazo, Eduardo Sastre-Perona, Ana Sánchez-Sánchez, Begoña Zamarrón, Ester |
| 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 |
| collection | Biblos-e Archivo. Repositorio Institucional de la UAM |
| 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 |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_5e7cca4e3cdf0cb516f340f75863d0bb |
| institution | Universidad Autónoma de Madrid |
| instname_str | Universidad Autónoma de Madrid |
| language | eng |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:repositorio.uam.es:10486/716560 |
| publishDate | 2021 |
| publishDateSort | 2021 |
| publisher | MDPI |
| publisherStr | MDPI |
| reponame_str | Biblos-e Archivo. Repositorio Institucional de la UAM |
| spelling | Intermittent hypoxia mediates paraspeckle protein-1 upregulation in sleep apnea 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 HIF1α Intermittent hypoxia Paraspeckle component 1 Sleep apnea TGFβ Medicina 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 This 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.) MDPI http://hdl.handle.net/10486/716560 https://dx.doi.org/10.3390/cancers13153888 |
| 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 | 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_short | Intermittent hypoxia mediates paraspeckle protein-1 upregulation in sleep apnea |
| title_sort | Intermittent hypoxia mediates paraspeckle protein-1 upregulation in sleep apnea |
| topic | HIF1α Intermittent hypoxia Paraspeckle component 1 Sleep apnea TGFβ Medicina |
| topic_facet | HIF1α Intermittent hypoxia Paraspeckle component 1 Sleep apnea TGFβ Medicina |
| url | http://hdl.handle.net/10486/716560 https://dx.doi.org/10.3390/cancers13153888 |