Endothelia cell-glucocorticoid receptor interactions and regulation of Wnt signaling
Endothelia cell-glucocorticoid receptor interactions and regulation of Wnt signaling
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DOI：
10.1172/jci.insight.131384
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发表时间：
2020-02-13
期刊：
影响因子：
8
通讯作者：
Goodwin, Julie E.
中科院分区：
文献类型：
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作者：
Zhou, Han;Mehta, Sameet;Goodwin, Julie E.
血管炎症存在于许多心血管疾病中，外源性糖皮质激素传统上被用作抑制炎症的疗法。然而，最近的数据表明，内源性糖皮质激素，通过内皮糖皮质激素受体，作为炎症的负调节剂。在这里，我们对糖皮质激素受体进行了ChIP，然后在小鼠内皮细胞中进行了下一代测序，以研究内皮糖皮质激素受体如何调节血管炎症。我们确定了Wnt信号通路在这种情况下的作用，并表明内皮糖皮质激素受体的损失导致Wnt信号在体外和体内使用我们验证的小鼠模型上调。此外，我们证明了糖皮质激素受体调控的Wnt途径中的一个关键基因，Frzb，通过糖皮质激素反应元件从我们的基因组数据收集。这些结果表明内皮Wnt信号转导调节在血管炎症状态中的作用。
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.