Pathological roles of advanced glycation end product receptors SR-A and CD36

Seikoh Horiuchi, Yuka Unno, Hitomi Usui, Kenichi Shikata, Kaori Takaki, Wakako Koito, Yu Ichiro Sakamoto, Ryoji Nagai, Kenji Makino, Akira Sasao, Jun Wada, Hirofumi Makino

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The pathological significance of advanced glycation end product (AGE)-modified proteins deposited in several lesions is generally accounted for by their cellular interaction via the AGE receptors and subsequent acceleration of the inflammatory process. In this study, we focused on two AGE receptors-specifically, the role of SR-A in pathogenesis of diabetic nephropathy and the role of CD36 in AGE-induced downregulation of leptin by adipocytes. In terms of SR-A, diabetic wild-type mice exhibited increased urinary albumin excretion, glomerular hypertrophy, and mesangial matrix expansion, whereas SR-A-knockout mice showed reduced glomerular size and mesangial matrix area. In these diabetic SR-A-knockout mice, the number of macrophages that infiltrated into glomeruli was remarkably reduced (P < 0.05), suggesting that SR-A-dependent glomerular migration of macrophages plays an important role in the pathogenesis of diabetic nephropathy. In terms of CD36, incubation of glycolaldehyde-modified bovine serum albumin (GA-BSA) with 3T3-L1 adipocytes reduced leptin secretion by these cells. The binding of GA-BSA to these cells and subsequent endocytic degradation were effectively inhibited by a neutralizing anti-CD36 antibody. AGE-induced downregulation of leptin was protected by N-acetyl-cysteine, an antioxidant. These results indicate that the interaction of AGE ligands with 3T3-L1 adipocytes via CD36 induces oxidative stress and leads to inhibition of leptin expression by these cells, suggesting a potential link of this phenomenon to exacerbation of the insulin sensitivity in metabolic syndrome.

Original languageEnglish
Pages (from-to)671-675
Number of pages5
JournalAnnals of the New York Academy of Sciences
Volume1043
DOIs
Publication statusPublished - 2005

Keywords

  • AGE receptor
  • Adipocytes
  • CD36
  • Leptin
  • Oxidized LDL
  • SR-A

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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