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Endothelial cell–glucocorticoid receptor interactions and regulation of Wnt signaling
Han Zhou, … , William C. Sessa, Julie E. Goodwin
Han Zhou, … , William C. Sessa, Julie E. Goodwin
Published February 13, 2020
Citation Information: JCI Insight. 2020;5(3):e131384. https://doi.org/10.1172/jci.insight.131384.
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Research Article Inflammation Vascular biology

Endothelial cell–glucocorticoid receptor interactions and regulation of Wnt signaling

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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.

Authors

Han Zhou, Sameet Mehta, Swayam Prakash Srivastava, Kariona Grabinska, Xinbo Zhang, Chris Wong, Ahmad Hedayat, Paola Perrotta, Carlos Fernández-Hernando, William C. Sessa, Julie E. Goodwin

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Figure 5

Detection of a potentially novel motif.

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Detection of a potentially novel motif.
(A) Heatmap of fold-expression c...
(A) Heatmap of fold-expression changes of 16 genes identified through advanced analysis of sequencing data. Trends are conserved for both GR replete and GR-KO conditions. (B) Potentially novel motif detected from analysis of 16 genes in A. (C) Luciferase assay showing fold induction for cells treated with media alone, RU486 alone for 4 hours, DEX alone for 4 hours, or RU486 4-hour pretreatment followed by 4 hours with DEX. Data represent 3 separate experiments. One-way ANOVA with Tukey’s post hoc test was used to analyze data. *P < 0.05.

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