Peroxisome proliferator-activated receptor-γ agonist rosiglitazone prevents albuminuria but not glomerulosclerosis in experimental diabetes.

Abstract

BACKGROUNDS/AIMS:

Renal inflammation and nephrin downregulation contribute to albuminuria in diabetes. We studied, in streptozotocin-induced diabetic rats, the effect of rosiglitazone (RSG), a peroxisome proliferator-activated receptor-γ agonist, on renal macrophage infiltration, MCP1, and nephrin expression in relation to albuminuria.

METHODS:

We investigated control and diabetic rats treated or untreated with RSG. Animals were sacrificed at 1, 3, and 9 months. Renal MCP1 and nephrin expression were studied by immunoblotting, renal macrophage infiltration by immunohistochemistry, and albuminuria by ELISA. Electron microscopy was used to assess glomerular ultrastructural morphology. In vitro experiments were conducted in isolated cultured rat glomeruli.

RESULTS:

Glycaemic control was similar in diabetic rats treated and untreated with RSG, and blood pressure was comparable in all groups. RSG prevented diabetes-induced albuminuria at 9 months, and renal macrophage infiltration and MCP1 upregulation at 3 and 9 months. Diabetes-mediated nephrin downregulation was abolished by RSG. Diabetes-induced glomerulosclerosis, glomerular basement membrane thickening, and foot process fusion were not affected by RSG. In isolated glomeruli, MCP1 directly induced nephrin downregulation and this was prevented by RSG. RSG had no effect on nephrin expression.

CONCLUSION:

RSG prevents albuminuria and nephrin downregulation in experimental diabetes independently of glycaemic and blood pressure control. This effect likely occurs via correction of diabetes-induced inflammatory processes.

• Authors: Giorgia Setti, Anthea Hayward, Cecile Dessapt, Francesca Barone, Robin Buckingham, Kathryn White, Rudolf Bilous, Kawachi Hiroshi, Gabriella Gruden, GianCarlo Viberti, Luigi Gnudi
• Journal: American journal of nephrology (Am J Nephrol) Vol. 32 Issue 5 Pg. 393-402 ( 2010) ISSN: 1421-9670 [Electronic] Switzerland
• PMID: 20814199 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 S. Karger AG, Basel.

Chemical References

• Chemokine CCL2
• Hypoglycemic Agents
• Membrane Proteins
• PPAR gamma
• Thiazolidinediones
• nephrin
• Rosiglitazone

Topics

• Albuminuria (drug therapy, prevention & control)
• Animals
• Cells, Cultured
• Chemokine CCL2 (metabolism, pharmacology)
• Diabetes Mellitus, Experimental (drug therapy, metabolism, pathology)
• Diabetic Nephropathies (drug therapy, metabolism, pathology)
• Hypoglycemic Agents (pharmacology, therapeutic use)
• Kidney (metabolism, pathology)
• Macrophages (drug effects)
• Male
• Membrane Proteins (metabolism)
• PPAR gamma (agonists)
• Rats
• Rats, Sprague-Dawley
• Rosiglitazone
• Thiazolidinediones (pharmacology, therapeutic use)