Osmotic Response Element Binding Protein is essential for water reabsorption in kidney

Abstract

In mammalian kidney, the osmolarity of the inner medulla is highly hypertonic. The cells protect themselves from shrinkage by the expression of a number of genes, such as AR and SMIT that increase the cellular levels of compatible osmolytes. The transcription of these genes is regulated by OREBP. Two independent lines of transgenic (Tg ) mice that overexpress the dominant-negative form of OREBP specifically in the collecting ducts were generated to study the physiological role of OREBP in the kidney. These Tg mice exhibited polyuria, polydipsia due to impaired urine concentrating ability. There was a reduction in the mRNA expression level of AQP-2, UTA-1 and UTA-2 in both renal medulla and renal epithelial cells of Tg mice but no change in the AQP-3 expression. However, during dehydration, Tg mice were able to concentrate their urine to ~30% of that in the non-Tg mice and there was up-regulation of AQP-2 and UTA-1 mRNA expression. Our data suggest that under normal physiological condition, OREBP plays an important role in water reabsorption in the kidney by regulating the expression of AQP-2, UTA-1 and UTA-2. Under dehydrated condition, increase of water reabsorption by the vasopressin/AQP2 system remains functional in the absence of OREBP. Furthermore, the Tg mice developed bilateral hydronephrosis progressively, suggesting that OREBP may also protect the renal cells against osmotic stress.