Expression of peroxisome proliferator-activated receptors in urinary tract of rabbits and humans

Abstract

Peroxisome proliferator-activated receptors (PPARs, alpha, beta/delta, and gamma) are members of the nuclear receptor superfamily of ligand-activated transcription factors. PPARs regulate the expression of genes involved in lipid metabolism. 8(S)-hydroxyeicosatetraenoic acid (8-S-HETE), leukotriene B4 (LTB4), and hypolipidemic fibrates activate PPAR alpha, whereas PPAR gamma is activated by prostaglandin metabolites. The present studies examined the intrarenal and tissue distribution of rabbit and human PPAR alpha, -beta/delta, and -gamma mRNAs. Nuclease protection showed PPAR alpha predominated in liver, heart, and kidney, whereas PPAR gamma, a putative adipose-specific transcription factor, was in white adipose tissue, bladder, and ileum, followed by kidney and spleen. Lower expression levels of PPAR beta/delta were observed in several tissues. In situ hybridization of kidney showed PPAR alpha mRNA predominated in proximal tubules and medullary thick ascending limbs of both rabbit and human. PPAR gamma was exclusively expressed in medullary collecting duct and papillary urothelium. Immunoblot confirmed the expression of PPAR gamma protein in freshly isolated inner medullary collecting ducts. mRNAs for all the PPARs were expressed in the ureter and bladder in both rabbit and human, but PPAR gamma expression was greatest. This distinct distribution of PPAR isoforms has important implications for lipid-activated gene transcription in urinary epithelia.