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In vascular smooth muscle cells paricalcitol prevents phosphate-induced Wnt/β-catenin activation
dc.contributor.author | Martínez-Moreno, Julio M. | |
dc.contributor.author | Muñoz-Castañeda, Juan R. | |
dc.contributor.author | Herencia, Carmen | |
dc.contributor.author | Montes de Oca, Addy | |
dc.contributor.author | Estepa Nieto, José Carlos | |
dc.contributor.author | Canalejo, Rocío | |
dc.contributor.author | Rodríguez-Ortiz, Maria E. | |
dc.contributor.author | Aguilera Tejero, Escolástico | |
dc.contributor.author | Canalejo, Antonio | |
dc.contributor.author | Rodríguez, Mariano | |
dc.contributor.author | Almadén Peña, Yolanda | |
dc.contributor.author | Pérez-Martínez, Pablo | |
dc.date.accessioned | 2017-11-23T08:26:15Z | |
dc.date.available | 2017-11-23T08:26:15Z | |
dc.date.issued | 2012 | |
dc.identifier.uri | http://hdl.handle.net/10396/15500 | |
dc.description.abstract | The present study investigates the differential effect of two vitamin D receptor agonists, calcitriol and paricalcitol, on human aortic smooth muscle cells calcification in vitro. Human vascular smooth muscle cells were incubated in a high phosphate (HP) medium alone or supplemented with either calcitriol 10−8M (HP + CTR) or paricalcitol 3·10−8 M (HP + PC). HP medium induced calcification, which was associated with the upregulation of mRNA expression of osteogenic factors such as bone morphogenetic protein 2 (BMP2), Runx2/Cbfa1, Msx2, and osteocalcin. In these cells, activation of Wnt/β-catenin signaling was evidenced by the translocation of β-catenin into the nucleus and the increase in the expression of direct target genes as cyclin D1, axin 2, and VCAN/versican. Addition of calcitriol to HP medium (HP + CTR) further increased calcification and also enhanced the expression of osteogenic factors together with a significant elevation of nuclear β-catenin levels and the expression of cyclin D1, axin 2, and VCAN. By contrast, the addition of paricalcitol (HP + PC) not only reduced calcification but also downregulated the expression of BMP2 and other osteoblastic phenotype markers as well as the levels of nuclear β-catenin and the expression of its target genes. The role of Wnt/β-catenin on phosphate- and calcitriol-induced calcification was further demonstrated by the inhibition of calcification after addition of Dickkopf-related protein 1 (DKK-1), a specific natural antagonist of the Wnt/β-catenin signaling pathway. In conclusion, the differential effect of calcitriol and paricalcitol on vascular calcification appears to be mediated by a distinct regulation of the BMP and Wnt/β-catenin signaling pathways. | es_ES |
dc.format.mimetype | application/pdf | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | American Journal of Physiology | es_ES |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/4.0/ | es_ES |
dc.source | AJP-Renal Physiology 303(8), F1136–F1144 (2012) | es_ES |
dc.subject | Vascular calcification | es_ES |
dc.subject | Calcitriol | es_ES |
dc.subject | Paricalcitol | es_ES |
dc.subject | VSMCs | es_ES |
dc.subject | Wnt/b-catenin | es_ES |
dc.title | In vascular smooth muscle cells paricalcitol prevents phosphate-induced Wnt/β-catenin activation | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.relation.publisherversion | http://dx.doi.org/10.1152/ajprenal.00684.2011 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/241544 (SYSKID) | es_ES |
dc.relation.projectID | Junta de Andalucía. JA 0127/2008 | es_ES |
dc.relation.projectID | Junta de Andalucía. CTS-5205 | es_ES |
dc.relation.projectID | Instituto de Salud Carlos III. FIS 10/1311 | es_ES |
dc.relation.projectID | Instituto de Salud Carlos III. FIS 11/02055 | es_ES |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es_ES |