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

Peroxisome proliferator-activated receptor-γ (PPARγ) is a nuclear transcription factor and the pharmacological 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 that 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, adipocyte fatty acid-binding protein (A-FABP), in renal glomerular cells and renal medullary microvascular endothelial cells, demonstrated by both 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 MC PPARγ can also drive PPARγ reporter. Troglitazone and 15-deoxy-Δ12,14 prostaglandin J₂ at low concentrations reduced mesangial cell [³H]thymidine incorporation without affecting viability. These data suggest that constitutive PPARγ activity exists in renal glomeruli in vivo and could provide a pharmacological target to directly modulate glomerular injury.