Rosiglitazone protects diabetic rats against kidney disease through the suppression of renal moncyte chemoattractant protein-1 expression

Abstract 

Although the pathogenetic mechanisms of diabetic nephropathy (DN) have not been elucidated thoroughly, an inflammatory mechanism has been suggested to contribute to its development and progression. Moncyte chemoattractant protein (MCP)-1 is a chemokine that can attract macrophages and T cells from the circulation to the local kidney, then activate them, and ultimately injure the renal tissue. Recent studies have demonstrated that thiazolidinediones decrease urinary albumin (ALB) excretion, which may be partly related to its anti-inflammatory action. Therefore, the effects of rosiglitazone on renal inflammation and renal injury were investigated in streptozotocin (STZ)-induced diabetic rats in this study. We examined the urinary excretion rates of ALB, retinal-binding protein (RBP), and MCP-1 of normal control group (Group C, n=8), STZ-induced diabetes mellitus group (Group D, n=8), and diabetes plus rosiglitazone (5 mg⋅kg^–1⋅day^–1) treatment group (Group R, n=8) at the eighth week. The renal tissues of diabetic rats were obtained for reverse transcriptase–polymerase chain reaction to examine the expression of MCP-1 mRNA. Our results showed that compared to normal control, urinary excretion rates of ALB, RBP, and MCP-1 were significantly increased in untreated diabetic rats at the eighth week. However, rosiglitazone treatment could markedly decrease all the parameters above. In addition, urinary excretion rate of MCP-1 showed positive correlations with urinary ALB excretion, urinary RBP excretion, and kidney/body weight. The expressions of MCP-1 mRNA in renal tissues were markedly up-regulated in untreated diabetic rats, and these could be notably reduced by rosiglitazone treatment. In conclusion, rosiglitazone may have a potential therapeutic target in DN, which may be partly attributed to lowering of the expression of MCP-1 in the local kidney and the urinary excretion of MCP-1.

Abbreviation: ALB, albumin, DN, diabetic nephropathy, FPG, fasting peripheral blood glucose, ICAM-1, intercellular adhesion molecule-1, IL-6, interleukin 6, MCP-1, moncyte chemoattractant protein-1, RBP, retinal-binding protein, STZ, streptozotocin, TECs, tubular epithelial cells, TZDs, thiazolidinediones, UAER, urinary albumin excretion rate

Keywords: Rosiglitazone, Diabetes mellitus, Diabetic mephropathy, Monocyte chemoattractant protein-1