Nuclear receptors in podocyte biology and glomerular disease

Nuclear receptors have important roles in normal physiological functions and in the pathophysiology of various diseases. Here, the authors focus on the roles of nuclear receptors in podocyte biology and non-diabetic glomerular disease as well as their potential as therapeutic targets. Nuclear receptors have a broad spectrum of biological functions in normal physiology and in the pathology of various diseases, including glomerular disease. The primary therapies for many glomerular diseases are glucocorticoids, which exert their immunosuppressive and direct podocyte protective effects via the glucocorticoid receptor (GR). As glucocorticoids are associated with important adverse effects and a substantial proportion of patients show resistance to these therapies, the beneficial effects of selective GR modulators are now being explored. Peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonism using thiazolidinediones has potent podocyte cytoprotective and nephroprotective effects. Repurposing of thiazolidinediones or identification of novel PPAR gamma modulators are potential strategies to treat non-diabetic glomerular disease. Retinoic acid receptor-alpha is the key mediator of the renal protective effects of retinoic acid, and repair of the endogenous retinoic acid pathway offers another potential therapeutic strategy for glomerular disease. Vitamin D receptor, oestrogen receptor and mineralocorticoid receptor modulators regulate podocyte injury in experimental models. Further studies are needed to better understand the mechanisms of these nuclear receptors, evaluate their synergistic pathways and identify their novel modulators. Here, we focus on the role of nuclear receptors in podocyte biology and non-diabetic glomerular disease.

Automated summary

Nuclear receptors play important roles in podocyte biology and non-diabetic glomerular disease, with potential as therapeutic targets.