title: Peroxisome proliferator-activated receptor-γ agonist rosiglitazone prevents albuminuria but not glomerulosclerosis in experimental diabetes.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Cardiovascular Division, King's College London, London, UK.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Setti
authors.forename: Anthea
authors.initials: A
authors.lastname: Hayward
authors.forename: Cecile
authors.initials: C
authors.lastname: Dessapt
authors.forename: Francesca
authors.initials: F
authors.lastname: Barone
authors.forename: Robin
authors.initials: R
authors.lastname: Buckingham
authors.forename: Kathryn
authors.initials: K
authors.lastname: White
authors.forename: Rudolf
authors.initials: R
authors.lastname: Bilous
authors.forename: Kawachi
authors.initials: K
authors.lastname: Hiroshi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gruden
authors.forename: GianCarlo
authors.initials: G
authors.lastname: Viberti
authors.forename: Luigi
authors.initials: L
authors.lastname: Gnudi
mesh_terms: D000419:Albuminuria / Q000188:drug therapy / Q000517:prevention & control*; D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018932:Chemokine CCL2; D007004:Hypoglycemic Agents; D008565:Membrane Proteins; D047495:PPAR gamma; D045162:Thiazolidinediones; C113267:nephrin; D000077154:Rosiglitazone