Nuclear hormone receptors in podocytes

Nuclear hormone receptors (NRs) belong to family of sequence specific and ligand activated transcription factors that both positively and negatively regulate gene expression and are involved in many developmental, cell survival, and endocrine functions in metabolism [1,2]. Consequently, aberrant NR signaling can lead to various reproductive, proliferative, and metabolic diseases. The ability of small molecule hormones to regulate NR activity make them excellent pharmaceutical targets; for example, retinoic acid (a ligand for retinoic acid receptor alpha, RARα), the synthetic antagonist tamoxifen (a ligand for estrogen receptor alpha, ERα), dexamethasone (a ligand for glucocorticoid receptor alpha, GRα) or thiazolidinediones (ligands for peroxisome proliferator-activated receptor gamma, PPARγ) are used in acute promyelocytic leukemia, ERα-positive breast cancer, inflammatory disorders and type II diabetes, respectively [3]. This family of hormones also plays important roles in the kidney development, in adult renal homeostasis and in disease responses. The kidney functions in the physiologic maintenance of acid–base and salt-water balance, and in removing toxins and metabolic waste while preserving nutrients in the bloodstream. The latter filtration function is largely mediated by the glomerular podocyte, a highly differentiated kidney cell that opposes the exterior of fenestrated capillaries in the renal glomerulus. Loss or injury of podocytes results in impaired blood filtration and causes many common renal diseases characterized by nephrotic syndrome. In this review, we will discuss the roles of NRs in normal podocyte development and in glomerular diseases and their physiological hormones and synthetic ligands as potential treatments for nephrotic syndrome.In humans, there are 48 NRs that can be broadly classified into four subfamilies based on their ligand binding, DNA binding and dimerization properties (Table 1). NRs bind to their DNA response elements either a