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dc.contributor.authorOller, Jorge
dc.contributor.authorAlfranca, Arántzazu
dc.contributor.authorMéndez-Barbero, Nerea
dc.contributor.authorVillahoz, Silvia
dc.contributor.authorLozano-Vidal, Noelia
dc.contributor.authorMartín-Alonso, Mara
dc.contributor.authorArroyo, Alicia G.
dc.contributor.authorEscolano, Amelia
dc.contributor.authorArmesilla, Angel Luis
dc.contributor.authorCampanero, Miguel R.
dc.contributor.authorRedondo, Juan Miguel
dc.date.accessioned2018-08-30T14:46:11Z
dc.date.available2018-08-30T14:46:11Z
dc.date.issued2015-09-04
dc.identifier.issn0270-7306
dc.identifier.issn1098-5549
dc.identifier.doi10.1128/MCB.00494-15
dc.identifier.urihttp://hdl.handle.net/2436/621661
dc.description.abstractEmerging evidence indicates that the metalloproteinase Adamts-1 plays a significant role in the pathophysiology of vessel remodeling, but little is known about the signaling pathways that control Adamts-1 expression. We show that vascular endothelial growth factor (VEGF), angiotensin-II, interleukin-1β, and tumor necrosis factor α, stimuli implicated in pathological vascular remodeling, increase Adamts-1 expression in endothelial and vascular smooth muscle cells. Analysis of the intracellular signaling pathways implicated in this process revealed that VEGF and angiotensin-II upregulate Adamts-1 expression via activation of differential signaling pathways that ultimately promote functional binding of the NFAT or C/EBPβ transcription factors, respectively, to the Adamts-1 promoter. Infusion of mice with angiotensin-II triggered phosphorylation and nuclear translocation of C/EBPβ proteins in aortic cells concomitantly with an increase in the expression of Adamts-1, further underscoring the importance of C/EBPβ signaling in angiotensin-II-induced upregulation of Adamts-1. Similarly, VEGF promoted NFAT activation and subsequent Adamts-1 induction in aortic wall in a calcineurin-dependent manner. Our results demonstrate that Adamts-1 upregulation by inducers of pathological vascular remodeling is mediated by specific signal transduction pathways involving NFAT or C/EBPβ transcription factors. Targeting of these pathways may prove useful in the treatment of vascular disease.
dc.language.isoen
dc.publisherAmerican Society for Microbiology
dc.subjectC/EBPBeta
dc.subjectADAMTS-1
dc.subjectNFAT
dc.subjectvascular remodeling
dc.titleC/EBPβ and Nuclear Factor of Activated T Cells Differentially Regulate Adamts-1 Induction by Stimuli Associated with Vascular Remodeling
dc.typeJournal article
dc.identifier.journalMolecular and Cellular Biology
dc.source.journaltitleMolecular and Cellular Biology
dc.source.volume35
dc.source.issue19
dc.source.beginpage3409
dc.source.endpage3422
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