PPARα Gene Expression in the Developing Rat Kidney: Role of Glucocorticoids

Abstract

Abstract. The α isoform of peroxisome proliferator-activated receptor (PPARα), which is highly expressed in the kidney, can stimulate the expression of genes that are involved in fatty acid catabolism and therefore might be involved in the control of renal fatty acid β-oxidation. PPARα expression and its regulation in the immature kidney are not well documented. This study delineated the developmental pattern of PPARα expression in the rat kidney cortex and the medulla between postnatal days 10 and 30 and investigated the role of glucocorticoids in regulating PPARα expression. In the cortex, PPARα mRNA and protein increased 2- and 1.8-fold, respectively, from 10 to 21 d and then decreased 1.5- and 2.4-fold from 21 to 30 d. In the medulla, PPARα mRNA and protein increased continuously 3.3- and 2.4-fold, respectively. It is shown here that acute treatment by dexamethasone of 10-d-old rats precociously induced a 4- to 6-fold increase in PPARα mRNA and a 1.8-fold increase in protein within 6 h in each part of the kidney. Chronic injection of dexamethasone for 3 d also increased PPARα mRNA 3.8- and 2.2-fold in the cortex and the medulla, respectively, with a 1.5- and 2-fold increase in protein. Furthermore, adrenalectomy prevented the increases in PPARα mRNA and protein in both the cortex and the medulla between postnatal days 16 and 21, and these could be restored by dexamethasone treatment. Finally, with the use of an established renal cell line, it was shown that glucocorticoids stimulate gene expression of PPARα and of medium chain acyl-CoA dehydrogenase (MCAD, a PPARα target gene) 2- to 4-fold and 1.5-fold, respectively, and that addition of fatty acids in the culture media led to a 2.2-fold increase in MCAD mRNA. Altogether, these results demonstrated that glucocorticoids are potent regulators of PPARα development in the immature kidney and that these hormones act in concert with fatty acids to regulate MCAD gene expression in renal cells.