Expression of peroxisomal proliferator-activated receptors and retinoid X receptors in the kidney

The discovery that 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is a ligand for the gamma-isoform of peroxisome proliferator-activated receptor (PPAR) suggests nuclear signaling by prostaglandins. Studies were undertaken to determine the nephron localization of PPAR isoforms and their heterodimer partners, retinoid X receptors (RXR), and to evaluate the function of this system in the kidney. PPAR alpha mRNA, determined by RT-PCR, was found predominately in cortex and further localized to proximal convoluted tubule (PCT); PPAR gamma was abundant in renal inner medulla, localized to inner medullary collecting duct (IMCD) and renal medullary interstitial cells (RMIC); PPAR beta, the ubiquitous form of PPAR, was abundant in all nephron segments examined. RXR alpha was localized to PCT and IMCD, whereas RXR beta was expressed in almost all nephron segments examined. mRNA expression of acyl-CoA synthase (ACS), a known PPAR target gene, was stimulated in renal cortex of rats fed with fenofibrate, but the expression was not significantly altered in either cortex or inner medulla of rats fed with troglitazone. In cultured RMIC cells, both troglitazone and 15d-PGJ(2) significantly inhibited cell proliferation and dramatically altered cell shape by induction of cell process formation. We conclude that PPAR and RXR isoforms are expressed in a nephron segment-specific manner, suggesting distinct functions, with PPAR alpha being involved in energy metabolism through regulating ACS in PCT and with PPAR gamma being involved in modulating RMIC growth and differentiation.