Peroxisome proliferator-activated receptor γ (PPARγ) activity is associated with the renal microvasculature

PPARγ is a nuclear transcription factor and the pharmacologic target for antidiabetic thiazolidinediones (TZDs). TZDs ameliorate diabetic nephropathy and have direct effects on cultured mesangial cells (MCs), however in situ hybridization failed to detect expression of PPARγ in glomeruli in vivo. The purpose of this study was to determine whether PPARγ is expressed in renal glomeruli. Two rabbit PPARγ isoforms were cloned. Nuclease protection assays demonstrate both PPARγ isoforms are expressed in freshly isolated glomeruli. Treatment of rabbits with the TZD, troglitazone, selectively induced expression of an endogenous PPARγ target gene, A-FABP, in renal glomerular cells and renal medullary microvascular endothelial cells demonstrated both by in situ hybridization and immunostain. Troglitazone also dramatically increased A-FABP expression in cultured MCs. Constitutive PPARγ expression was detected in cultured rabbit MCs. Endogenous mesangial cell PPARγ can also drive PPARγ reporter. Troglitazone and 15dPGJ 2 at low concentrations reduced mesangial cell 3 H-thymidine incorporation without affecting viability. These data suggest that constitutive PPARγ activity exists in renal glomeruli in vivo and could provide a pharmacologic target to directly modulate glomerular injury.