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Am J Physiol Renal Physiol 281: F1036-F1046, 2001. First published July 12, 2001; doi:10.1152/ajprenal.0025.2001
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Vol. 281, Issue 6, F1036-F1046, December 2001

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

Youfei Guan1, Yahua Zhang1, André Schneider1, Linda Davis1, Richard M. Breyer2, and Matthew D. Breyer1,3

1 Division of Nephrology, Department of Medicine, and Departments of 3 Molecular Physiology and Biophysics and 2 Pharmarcology, Vanderbilt University Medical Center, Nashville, Tennessee 37212

First published July 12, 2001; 10.1152/ajprenal.00025.2001.---Peroxisome proliferator-activated receptor-gamma (PPARgamma ) 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 PPARgamma in glomeruli in vivo. The purpose of this study was to determine whether PPARgamma is expressed in renal glomeruli. Two rabbit PPARgamma isoforms were cloned. Nuclease protection assays demonstrate that both PPARgamma isoforms are expressed in freshly isolated glomeruli. Treatment of rabbits with the TZD troglitazone selectively induced expression of an endogenous PPARgamma 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 PPARgamma expression was detected in cultured rabbit MCs. Endogenous MC PPARgamma can also drive PPARgamma reporter. Troglitazone and 15-deoxy-Delta 12,14 prostaglandin J2 at low concentrations reduced mesangial cell [3H]thymidine incorporation without affecting viability. These data suggest that constitutive PPARgamma activity exists in renal glomeruli in vivo and could provide a pharmacological target to directly modulate glomerular injury.

glomeruli; mesangial cell; adipocyte fatty acid-binding protein


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