Pigment-epithelium-derived factor suppresses expression of receptor for advanced glycation end products in the eye of diabetic rats

Sho Ichi Yamagishi, Takanori Matsui, Kazuo Nakamura, Takafumi Yoshida, Masayoshi Takeuchi, Hiroyoshi Inoue, Yumiko Yoshida, Tsutomu Imaizumi

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

The interaction of advanced glycation end products (AGEs) and their receptor (RAGE) elicits inflammatory and proliferative responses in retinal vascular wall cells, thereby being involved in the pathogenesis of diabetic retinopathy. Recently, pigment-epithelium-derived factor (PEDF) has also been shown to play a role in diabetic retinopathy. However, the effects of PEDF on RAGE gene expression remain to be elucidated. Therefore, we investigated here whether PEDF could prevent diabetes- or AGE-induced RAGE gene expression and the way that it might achieve this effect. Administration of PEDF or pyridoxal phosphate, an AGE inhibitor, suppressed RAGE gene expression in the eye of streptozotocin-induced diabetic rats. Further, intravenous injection of AGEs to normal rats increased RAGE gene expression, which was also blocked by PEDF. In vitro, PEDF or an antioxidant N-acetylcysteine blocked the AGE-induced RAGE gene induction in microvascular endothelial cells. In addition, PEDF completely inhibited superoxide generation and NF-κB activation in AGE-exposed endothelial cells. These results demonstrated that PEDF could inhibit diabetes- or AGE-induced RAGE gene expression by blocking the superoxide-mediated NF-κB activation. Our present study suggests that pharmacological upregulation or substitution of PEDF may play a protective role against diabetic retinopathy by attenuating the deleterious effect of AGEs.

Original languageEnglish
Pages (from-to)92-97
Number of pages6
JournalOphthalmic research
Volume39
Issue number2
DOIs
Publication statusPublished - 2007 Mar 1
Externally publishedYes

Keywords

  • Advanced glycation end products
  • Diabetic retinopathy
  • Oxidative stress
  • Pigment-epithelium-derived factor
  • Receptor for advanced glycation end products

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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