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dc.contributor.authorMorgado-Pascual, José L.
dc.contributor.authorRayego Mateos, Sandra
dc.contributor.authorValdivielso Revilla, José Manuel
dc.contributor.authorOrtiz, Alberto
dc.contributor.authorEgido, Jesús
dc.contributor.authorRuiz-Ortega, Marta
dc.date.accessioned2015-09-14T11:34:47Z
dc.date.available2015-09-14T11:34:47Z
dc.date.issued2015
dc.identifier.issn2314-6133
dc.identifier.urihttp://hdl.handle.net/10459.1/48700
dc.description.abstractChronic kidney disease is characterized by Vitamin D deficiency and activation of the renin-angiotensin-aldosterone system. Increasing data show that vitamin D receptor agonists (VDRAs) exert beneficial effects in renal disease and possess anti-inflammatory properties, but the underlying mechanism remains unknown. Emerging evidence suggests that “a disintegrin and metalloproteinase” (ADAM)/epidermal growth factor receptor (EGFR) signalling axis contributes to renal damage. Aldosterone induces EGFR transactivation regulating several processes including cell proliferation and fibrosis. However, data on tubular epithelial cells is scarce. We have found that, in cultured tubular epithelial cells, aldosterone induced EGFR transactivation via TGF-α/ADAM17. Blockade of the TGF-α/ADAM17/EGFR pathway inhibited aldosterone-induced proinflammatory gene upregulation. Moreover, among the potential downstream mechanisms, we found that TGF-α/ADAM17/EGFR inhibition blocked ERK and STAT-1 activation in response to aldosterone. Next, we investigated the involvement of TGF-α/ADAM17/EGFR axis in VDRA anti-inflammatory effects. Preincubation with the VDRA paricalcitol inhibited aldosterone-induced EGFR transactivation, TGF-α/ADAM-17 gene upregulation, and downstream mechanisms, including proinflammatory factors overexpression. In conclusion, our data suggest that the anti-inflammatory actions of paricalcitol in tubular cells could depend on the inhibition of TGF-α/ADAM17/EGFR pathway in response to aldosterone, showing an important mechanism of VDRAs action.ca_ES
dc.description.sponsorshipThis work was supported by grants from the Instituto de Salud Carlos III (ISCIIIRETIC REDINREN RD12, PI11/ 01854, PI041/00041, PI13/00047, PIE13/00051, and PI0/ 00072), Comunidad de Madrid (Fibroteam S2010/BMD-232; CIFRA S2010/BMD-2378), Sociedad Española de Nefrología, European Network (FP7-HEALTH-2013-INNOVATION-1- 602422), and Programa Intensificación Actividad Investigadora (ISCIII/Agencia Laín-Entralgo/CM) to Alberto Ortiz.
dc.language.isoengca_ES
dc.publisherHindawi Publishing Corporationca_ES
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1155/2015/783538ca_ES
dc.relation.ispartofBioMed Research International, 2015, ID 783538, p. 1-13ca_ES
dc.rightscc-by (c) Morgado-Pascual, José L. et al., 2015ca_ES
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es/*
dc.subject.otherVitamina Dca_ES
dc.subject.otherRonyons -- Malaltiesca_ES
dc.titleParicalcitol Inhibits Aldosterone-Induced Proinflammatory Factors by Modulating Epidermal Growth Factor Receptor Pathway in Cultured Tubular Epithelial Cellsca_ES
dc.typearticleca_ES
dc.identifier.idgrec023881
dc.type.versionpublishedVersionca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_ES
dc.identifier.doihttps://doi.org/10.1155/2015/783538
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/602422


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cc-by (c) Morgado-Pascual, José L. et al., 2015
Except where otherwise noted, this item's license is described as cc-by (c) Morgado-Pascual, José L. et al., 2015