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Genomic landscape of endothelial cell-glucocorticoid receptor interactions: Regulation of the Wnt signaling pathway

ABSTRACT: Genomic landscape of endothelial cell-glucocorticoid receptor interactions: Regulation of the Wnt signaling pathway

PROVIDER: PRJNA488077 | ENA |

REPOSITORIES: ENA

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Genomic landscape of endothelial cell-glucocorticoid receptor interactions: Regulation of the Wnt signaling pathway [RNA-seq]

Project description:Vascular inflammation is present in many cardiovascular diseases and exogenous glucocorticoids have traditionally been used as a therapy to suppress inflammation. However, recent data has shown that endogenous glucocorticoids, acting through the endothelial glucocorticoid receptor, act as negative regulators of inflammation. Here we performed chromatin immunoprecipitation for the glucocorticoid receptor followed by next-gen sequencing in mouse endothelial cells to investigate how the endothelial glucocorticoid receptor regulates vascular inflammation. We identified a novel role of the Wnt signaling pathway in this setting and show that loss of the endothelial glucocorticoid receptor results in up regulation of Wnt signaling both in vitro and in vivo using our validated mouse model. Further we demonstrate glucocorticoid receptor regulation of a key gene in the Wnt pathway via a novel glucocorticoid response element gleaned from our genomic data. These results suggest a novel role for endothelial Wnt signaling modulation in states of vascular inflammation.

2020-04-07 | GSE119092 | GEO

Genomic landscape of endothelial cell-glucocorticoid receptor interactions: Regulation of the Wnt signaling pathway [ChIP-seq]

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Genomic landscape of endothelial cell-glucocorticoid receptor interactions: Regulation of the Wnt signaling pathway [RNA-seq]

Project description:Genomic landscape of endothelial cell-glucocorticoid receptor interactions: Regulation of the Wnt signaling pathway [RNA-seq]

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Genomic landscape of endothelial cell-glucocorticoid receptor interactions: Regulation of the Wnt signaling pathway [ChIP-seq]

Project description:Genomic landscape of endothelial cell-glucocorticoid receptor interactions: Regulation of the Wnt signaling pathway [ChIP-seq]

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Genomic landscape of endothelial cell-glucocorticoid receptor interactions: Regulation of the Wnt signaling pathway

Project description:This SuperSeries is composed of the SubSeries listed below.

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Project description: Not available

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Project description: Not available

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Project description:The Wnt signaling pathway is one of the most ancient and pivotal signaling cascades, governing diverse processes in development and cancer regulation. Within the realm of cancer treatment, genistein emerges as a promising candidate due to its multifaceted modulation of various signaling pathways, including the Wnt pathway. Despite promising preclinical studies, the precise mechanisms underlying genistein's therapeutic effects via Wnt modulation remain elusive. In this study, we unveil novel insights into the therapeutic mechanisms of genistein by elucidating its inhibitory effects on Wnt signaling through macropinocytosis. Additionally, we demonstrate its capability to curtail cell growth, proliferation, and lysosomal activity in the SW480 colon adenocarcinoma cell model. Furthermore, our investigation extends to the embryonic context, where genistein influences gene regulatory networks governed by endogenous Wnt pathways. Our findings shed light on the intricate interplay between genistein, Wnt signaling, membrane trafficking, and gene regulation, paving the way for further exploration of genistein's therapeutic potential in cancer treatment strategies.

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