Role of Endothelial Glucocorticoid Receptor in the Pathogenesis of Kidney Diseases

Figures

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  Figure 1. Selected effects of GR signalling in endothelial cells and its implication in kidney health and disease. Effect of GR signalling on various aspects of endothelial cell function showing inhibition of proinflammatory MAPK, NF-κB, AP1 and Wnt pathways as well as effect on vascular tone and VEGF-VEGFR1. “(−)” representing inhibition and (+) stimulatory effect. GCs lead transrepression of inflammatory genes such as NF-κB or AP-1 in endothelium. GR stimulation activates MPK-1 phosphatase and inhibits MAPK pathway and E-selectin expression. GCs can induce TLR 2 and 4, and NLRP3 genes. GCs can reduce VEGF and VEGF receptor 1 (VEGFR1) protein expression through the mTORC1 pathway. GR stimulation is associated with inhibition of the Wnt/β-catenin pathway. GCs can increase the secretion of ET-1 and AT-2 from ECs. GCs directly reduce eNOS transcription through GATA interaction. GCs reduce expression of adhesion molecules on endothelial cells. VEGF—vascular endothelial growth factor, VEGFR-1—vascular endothelial growth factor receptor 1, eNOS—endothelial nitric oxide synthase, ET-1—endothelin 1, AT-II—angiotensin II, MAPK—mitogen activated protein kinases, NF-κB—nuclear factor kappa B,…

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  Figure 2. Podocyte–endothelial crosstalk and its potential connection with GR signalling. Figure shows podocyte and endothelial cell with glomerular base membrane between them. Podocytes produce VEGF, angiopoietins, semaphorins and SDF-1 which are secreted and influence endothelial cells homeostasis. ECs might secrete APC which protects podocytes against apoptosis. GR stimulation might impair VEGF signalling and influence podocyte Wnt/β catenin pathway and promote FAO. Lack of GR stimulation in podocytes might damage ECs through unknown mediator. APC—activated protein C, EC—endothelial cell, FAO—fatty acid oxidation, GBM—glomerular base membrane, SDF-1—Stromal cell-derived factor 1 VEGF—vascular endothelial growth factor, VEGF-R—vascular endothelial growth factor receptor, Wnt—Wnt signalling pathway.