Regulation of aldose reductase gene expression in renal cortex and medulla of rats

Abstract

A role for aldose reductase-mediated production of polyol in the aetiology of diabetic nephropathy has been supported by both animal and clinical studies. In the renal medulla, the rate of polyol production is influenced in part by regulated changes in the level of aldose reductase gene expression. However, little is known about the expression of aldose reductase in the renal cortex. In this study, we evaluated the regulation of aldose reductase gene expression in the renal cortex and medulla in response to galactose feeding. Four groups of rats (n = 6) were treated for 9 weeks with control or galactose diet in the presence or absence of sorbinil, an aldose reductase inhibitor. In the renal medulla, galactose treatment produced a significant (p < 0.01) decrease in aldose reductase mRNA, to approximately 10% of control levels. Coadministration of sorbinil partially prevented the effect of galactose feeding on medullary aldose reductase mRNA (to 43% of control). Under basal conditions, the concentration of aldose reductase mRNA in the cortex was only 1% that of the renal medulla. Galactose feeding significantly reduced cortical aldose reductase mRNA by 29% relative to control (p < 0.01), and this was completely reversed by addition of sorbinil. Sorbinil administration to rats fed a control diet also decreased aldose reductase expression in the renal medulla and cortex. These results demonstrate that galactose feeding results in dynamic, polyol-dependent regulation of aldose reductase gene expression in the renal cortex as well as the medulla.(ABSTRACT TRUNCATED AT 250 WORDS)