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C/EBPβ and nuclear factor of activated T cells differentially regulate Adamts-1 induction by stimuli associated with vascular remodeling

AuthorsOller, Jorge; Alfranca, Arántzazu; Méndez-Barbero, Nerea; Campanero, Miguel R. ; Redondo, Juan Miguel
Issue Date2015
PublisherAmerican Society for Microbiology
CitationMolecular and Cellular Biology 35(19): 3409-3422 (2015)
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.
Descriptionet al.
Publisher version (URL)https://doi.org/10.1128/MCB.00494-15
Identifiersdoi: 10.1128/MCB.00494-15
issn: 0270-7306
e-issn: 1098-5549
Appears in Collections:(IIBM) Artículos
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