Telmisartan, an angiotensin II type 1 receptor blocker, inhibits advanced glycation end-product (AGE)-induced monocyte chemoattractant protein-1 expression in mesangial cells through downregulation of receptor for AGEs via peroxisome proliferator-activated receptor-γ, activation

T. Matsui, Shoichi Yamagishi, S. Ueda, K. Nakamura, T. Imaizumi, M. Takeuchi, H. Inoue

Research output: Contribution to journalArticle

60 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)482-489
Number of pages8
JournalJournal of International Medical Research
Volume35
Issue number4
DOIs
Publication statusPublished - 2007 Jan 1
Externally publishedYes

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Keywords

  • Advanced glycation end-products (AGEs)
  • Candesartan
  • Diabetic nephropathy
  • GW9662
  • Monocyte chemoattractant protein-1 (MCP-1)
  • Peroxisome proliferator-activated receptor-γ (PPAR-γ) oxidative stress
  • Telmisartan

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Biochemistry, medical

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