Renal epidermal growth factor receptor: Its role in sodium and water homeostasis in diabetic nephropathy

Abstract

Volume expansion is observed in animal and human models of diabetic nephropathy, which is in a large part a result of disordered renal tubular cell sodium and water transport. Sodium transport in the proximal tubule is increased in diabetes mellitus as a result of enhanced activity of the sodium-hydrogen exchanger-3 (NHE3), the key transporter for transcellular reabsorption of sodium. Transactivation of the epidermal growth factor receptor (EGFR) by factors inherent in the milieu of diabetes mellitus increases serum glucocorticoid regulated kinase-1 (Sgk1), a key regulator of NHE3. Enhanced sodium and water reabsorption, occurring as a consequence of endogenous or pharmacological stimulation of the peroxisome proliferator-activated receptor gamma is Sgk1 mediated. EGFR inhibitors, which are currently used clinically to treat malignancies, might have potential in attenuating the cellular mechanisms responsible for thiazolidinedione (TZD)-mediated sodium and water transport in diabetes. In the present review, the authors focus on the importance of the EGFR in sodium and water uptake in the proximal tubule in the environment of pathophysiological and pharmacological influences. © 2011 The Authors. Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.