Role of endothelial glucocorticoid receptor in the pathogenesis of kidney diseases

Abstract

Glucocorticoids, as multifunctional hormones, are widely used in the treatment of various diseases including nephrological disorders. They are known to affect immunological cells, effectively treating many autoimmune and inflammatory processes. Furthermore, there is a growing body of evidence demonstrating the potent role of glucocorticoids in non-immune cells such as podocytes. Moreover, novel data show additional pathways and processes affected by glucocorticoids, such as the Wnt pathway or autophagy. The endothelium is currently considered as a key organ in the regulation of numerous kidney functions such as glomerular filtration, vascular tone and the regulation of inflammation and coagulation. In this review, we analyse the literature concerning the effects of endothelial glucocorticoid receptor signalling on kidney function in health and disease, with special focus on hypertension, diabetic kidney disease, glomerulopathies and chronic kidney disease. Recent studies demonstrate the potential role of endothelial GR in the prevention of fibrosis of kidney tissue and cell metabolism through Wnt pathways, which could have a protective effect against disease progression. Another important aspect covered in this review is blood pressure regulation though GR and eNOS. We also briefly cover potential therapies that might affect the endothelial glucocorticoid receptor and its possible clinical implications, with special interest in selective or local GR stimulation and potential mitigation of GC treatment side effects.