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This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2005111196v1 17/5/1362    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Han, S.-Y. Articles by Cha, D.-R. Search for Related Content PubMed PubMed Citation Articles by Han, S.-Y. Articles by Cha, D.-R. Related Collections Related Article

Spironolactone Prevents Diabetic Nephropathy through an Anti-Inflammatory Mechanism in Type 2 Diabetic Rats

Sang-Youb Han^*,, Cy-Hyun Kim, Han-Seong Kim, Yi-Hwa Jee, Hye-Kyoung Song, Mi-Hwa Lee, Kum-Hyun Han, Hyoung-Kyu Kim, Young-Sun Kang, Jee-Young Han^||, Young-Sik Kim^¶ and Dae-Ryong Cha

^* Department of Internal Medicine, Clinical Research Center, and Department of Pathology, Inje University, Ilsan-Gu, Goyang City, and Departments of Internal Medicine and ^¶ Pathology, Korea University, Ansan City, Kyungki-Do, and ^|| Department of Pathology, Inha University, Chung-Gu, Sinheung-dong, Chung-Gu, Incheon, Korea

Address correspondence to: Dr. Dae Ryong Cha, Department of Internal Medicine, Korea University Ansan Hospital, 516 Kojan-Dong, Ansan City, Kyungki-Do, 425-020, Korea. Phone: +82-31-412-6590; Fax: +82-31-412-5574; E-mail: cdragn{at}unitel.co.kr

Received for publication November 18, 2005. Accepted for publication February 7, 2006.

Aldosterone induces myocardial fibrosis and vascular inflammation via proinflammatory and profibrotic cytokines. The effect of spironolactone on renal inflammation and renal function was investigated in type 2 diabetic rats. For define the molecular mechanism of spironolactone, the effect of spironolactone on the synthesis of monocyte chemotactic peptide-1 (MCP-1) and its upstream transcription factor, NF-B, was evaluated in cultured mesangial cells and proximal tubular cells. There were no changes in blood glucose concentration or BP after spironolactone treatment. Spironolactone treatment significantly reduced urinary albumin excretion and ameliorated glomerulosclerosis. Urinary levels of MCP-1 were significantly increased concurrently with renal expression of MCP-1, macrophage migration inhibitory factor, and macrophage infiltration. Spironolactone treatment significantly inhibited urinary excretion of MCP-1 as well as renal MCP-1 and migration inhibitory factor expression and macrophage infiltration. In addition, aldosterone induced upregulation of MCP-1 expression and NF-B transcriptional activity in cultured cells, and spironolactone reduced both NF-B activation and MCP-1 synthesis. Furthermore, NF-B inhibition abolished aldosterone-induced MCP-1 production. Overall, these findings suggest that aldosterone-induced NF-B activation leads to activation of proinflammatory cytokines, ultimately leading to renal injury in this model. These data suggest that mineralocorticoid blockade may be a potential therapeutic target in diabetic nephropathy.

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