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 recept or (PPAR) suggests nuclear signaling by prostaglandins. Studies were undert aken to determine the nephron localization of PPAR isoforms and their heter odimer partners, retinoid X receptors (RXR), and to evaluate the function o f this system in the kidney. PPAR alpha mRNA, determined by RT-PCR, was fou nd predominately in cortex and further localized to proximal convoluted tub ule (PCT); PPAR gamma was abundant in renal inner medulla, localized to inn er 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 be ta was expressed in almost all nephron segments examined. mRNA expression o f acyl-CoA synthase (ACS), a known PPAR target gene, was stimulated in rena l cortex of rats fed with fenofibrate, but the expression was not significa ntly altered in either cortex or inner medulla of rats fed with troglitazon e. In cultured RMIC cells, both troglitazone and 15d-PGJ(2) significantly i nhibited cell proliferation and dramatically altered cell shape by inductio n of cell process formation. We conclude that PPAR and RXR isoforms are exp ressed 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 di fferentiation.