Endothelial cell–glucocorticoid receptor interactions and regulation of Wnt signaling
Open Access
- 13 February 2020
- journal article
- research article
- Published by American Society for Clinical Investigation in JCI Insight
Abstract
Vascular inflammation is present in many cardiovascular diseases, and exogenous glucocorticoids have traditionally been used as a therapy to suppress inflammation. However, recent data have shown that endogenous glucocorticoids, acting through the endothelial glucocorticoid receptor, act as negative regulators of inflammation. Here, we performed ChIP for the glucocorticoid receptor, followed by next-generation sequencing in mouse endothelial cells to investigate how the endothelial glucocorticoid receptor regulates vascular inflammation. We identified a role of the Wnt signaling pathway in this setting and show that loss of the endothelial glucocorticoid receptor results in upregulation of Wnt signaling both in vitro and in vivo using our validated mouse model. Furthermore, we demonstrate glucocorticoid receptor regulation of a key gene in the Wnt pathway, Frzb, via a glucocorticoid response element gleaned from our genomic data. These results suggest a role for endothelial Wnt signaling modulation in states of vascular inflammation.Funding Information
- NHLBI (R01 HL131952)
This publication has 50 references indexed in Scilit:
- Secreted Wnt Modulators in Symptomatic Aortic StenosisJournal of the American Heart Association, 2012
- Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and CufflinksNature Protocols, 2012
- Hemodynamic Activation of β-Catenin and T-Cell-Specific Transcription Factor Signaling in Vascular Endothelium Regulates Fibronectin ExpressionArteriosclerosis, Thrombosis, and Vascular Biology, 2011
- The value of position-specific priors in motif discovery using MEMEBMC Bioinformatics, 2010
- Estrogen receptor signaling promotes dendritic cell differentiation by increasing expression of the transcription factor IRF4Blood, 2010
- Genomic determination of the glucocorticoid response reveals unexpected mechanisms of gene regulationGenome Research, 2009
- Inhibition of NF-κB-dependent Transcription by MKP-1Online Journal of Public Health Informatics, 2009
- TopHat: discovering splice junctions with RNA-SeqBioinformatics, 2009
- Model-based Analysis of ChIP-Seq (MACS)Genome Biology, 2008
- Regulation of the Rat UGT1A6 by Glucocorticoids Involves a Cryptic Glucocorticoid Response ElementDrug Metabolism and Disposition, 2007