Authors: Matsui, T.¹; Yamagishi, S.¹; Ueda, S.¹; Nakamura, K.¹; Imaizumi, T.¹; Takeuchi, M.²; Inoue, H.³

Source: The Journal of International Medical Research, Volume 35, Number 4, July 2007 , pp. 482-489(8)

Publisher: Field House Publishing

Abstract:

Interaction between advanced glycation end-products (AGEs) and their receptor (RAGE) plays a central role in diabetic nephropathy pathogenesis. Pathophysiological crosstalk between the AGEs-RAGE system and angiotensin II (Ang II) is also involved in this disease. This study investigated the role of proliferator-activated receptor-γ (PPAR-γ)-modulating activity on inhibition of monocyte chemoattractant protein (MCP-1) expression. Telmisartan, an Ang II type 1 receptor blocker, downregulated RAGE mRNA and inhibited superoxide generation and MCP-1 gene expression in mesangial cells; these processes were blocked by GW9662, a PPAR-γ inhibitor. Candesartan, an Ang II type 1 receptor blocker, did not suppress AGEs-induced superoxide generation. Telmisartan and the antioxidant, N-acetylcysteine, completely inhibited AGEs-induced MCP-1 overproduction by mesangial cells. These results suggest that telmisartan inhibits AGEs-signalling to MCP-1 expression in mesangial cells by downregulating RAGE gene expression and subsequent oxidative stress generation via PPAR-γ activation. This study has demonstrated a unique benefit of telmisartan in that it may function as an anti-inflammatory agent against AGEs via PPAR-γ activation and may play a protective role in diabetic nephropathy.

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Keywords: TELMISARTAN; CANDESARTAN; GW9662; ADVANCED GLYCATION END-PRODUCTS (AGES); DIABETIC NEPHROPATHY; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA (; MONOCYTE CHEMOATTRACTANT PROTEIN-1 (MCP-1)

Document Type: Research article

Affiliations: 1: Department of Medicine, Institute for Basic and Clinical Medicine, Kurume University School of Medicine, Kurume, Japan 2: Department of Pathophysiological Science, Faculty of Pharmaceutical Science, Hokuriku University, Kanazawa, Japan 3: Department of Radioisotopes, Institute for Basic and Clinical Medicine, Kurume University School of Medicine, Kurume, Japan

Publication date: 2007-07-01

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