Expression and Function of Peroxisome Proliferator–Activated Receptor-γ in Mesangial Cells
Open Access
- 1 February 2001
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hypertension
- Vol. 37 (2), 722-727
- https://doi.org/10.1161/01.hyp.37.2.722
Abstract
Peroxisome proliferator–activated receptor-γ (PPARγ) is a novel nuclear receptor, which enhances insulin-mediated glucose uptake. Ligands to PPARγ are currently used as therapy for type II diabetes. Using Western blot analysis, RNase protection assay, and immunostaining, we identified the presence of PPARγ message and protein in cultured primary rat mesangial cells. Electrophoretic mobility of a labeled PPARγ response element (PPRE) was retarded in the presence of mesangial cell nuclear extract, suggesting that PPARγ is functional in these cells. The addition of unlabeled PPRE efficiently competed away the PPARγ-PPRE protein complex, confirming specificity of binding of the PPARγ to the PPRE. PPARγ ligands rosiglitazone (1 to 10 μmol/L) and troglitazone (1 to 10 μmol/L) inhibited platelet-derived growth factor–induced DNA synthesis, measured as bromodeoxyuridine incorporation (P P <0.05) but did not affect hyperglycemia or blood pressure in this model. This treatment also decreased glomerular plasminogen activator inhibitor-1 (PAI-1) expression. These data suggest that PPARγ activation may directly attenuate diabetic glomerular disease, possibly by inhibiting mesangial growth, which occurs early in the process of diabetic nephropathy, or by inhibiting PAI-1 expression. PAI-1 inhibits the activation of plasmin and matrix metalloproteinase, which degrade extracellular matrix in the glomerulus. Excess glomerular PAI-1 allows the accumulation of extracellular matrix, leading to glomerulosclerosis. These results have therapeutic implications for diabetic nephropathy as well as for proliferative mesangial diseases of the kidney.Keywords
This publication has 31 references indexed in Scilit:
- Peroxisome Proliferator-activated Receptor γ Ligands Inhibit Retinoblastoma Phosphorylation and G1 → S Transition in Vascular Smooth Muscle CellsJournal of Biological Chemistry, 2000
- Peroxisome proliferator-activated receptor γ1 (PPARγ1) expresses in rat mesangial cells and PPARγ agonists modulate its differentiationBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2000
- Thiazolidinediones Down-Regulate Plasminogen Activator Inhibitor Type 1 Expression in Human Vascular Endothelial Cells: A Possible Role for PPARγ in Endothelial FunctionBiochemical and Biophysical Research Communications, 1999
- Dual effects of angiotensin II on the plasminogen/plasmin system in rat mesangial cellsKidney International, 1997
- Modulation of plasminogen activator inhibitor-1 in vivo: A new mechanism for the anti-fibrotic effect of renin-angiotensin inhibitionKidney International, 1997
- Insulin and angiotensin II are additive in stimulating TGF-β1 and matrix mRNAs in mesangial cellsKidney International, 1996
- Cellular events in the evolution of experimental diabetic nephropathyKidney International, 1995
- Angiotensin II stimulates extracellular matrix protein synthesis through induction of transforming growth factor-beta expression in rat glomerular mesangial cells.JCI Insight, 1994
- Control of the peroxisomal β-oxidation pathway by a novel family of nuclear hormone receptorsCell, 1992
- Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferatorsNature, 1990