Peroxisome proliferator-activated receptor-gamma activity is associated with renal microvasculature

Peroxisome proliferator-activated receptor-gamma (PPAR gamma) is a nuclear transcription factor and the pharmacological target for antidiabetic thiazo lidinediones (TZDs). TZDs ameliorate diabetic nephropathy and have direct e ffects on cultured mesangial cells (MCs); however, in situ hybridization fa iled to detect expression of PPAR gamma in glomeruli in vivo. The purpose o f this study was to determine whether PPAR gamma is expressed in renal glom eruli. Two rabbit PPAR gamma isoforms were cloned. Nuclease protection assa ys demonstrate that both PPAR gamma isoforms are expressed in freshly isola ted glomeruli. Treatment of rabbits with the TZD troglitazone selectively i nduced expression of an endogenous PPAR gamma target gene, adipocyte fatty acid-binding protein (A-FABP), in renal glomerular cells and renal medullar y microvascular endothelial cells, demonstrated by both in situ hybridizati on and immunostain. Troglitazone also dramatically increased A-FABP express ion in cultured MCs. Constitutive PPAR gamma expression was detected in cul tured rabbit MCs. Endogenous MC PPAR gamma can also drive PPAR gamma report er. Troglitazone and 15-deoxy-Delta 12,14 prostaglandin J(2) at low concent rations reduced mesangial cell [H-3] thymidine incorporation without affect ing viability. These data suggest that constitutive PPAR gamma activity exi sts in renal glomeruli in vivo and could provide a pharmacological target t o directly modulate glomerular injury.