Inhibition by advanced glycation end products (AGEs) of pigment epithelium-derived factor (PEDF) gene expression in microvascular endothelial cells

S. Yamagishi, T. Matsui, Hiroyoshi Inoue

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Pigment epithelium-derived factor (PEDF) is a natural extracellular component of the retina with neuronal differentiating activity. Recently, decreased levels of PEDF in the mammalian eye have been shown to participate in the pathogenesis of diabetic retinopathy. In addition, advanced glycation end products (AGEs), senescent macroprotein derivatives that form at an accelerated rate under diabetes, have also been implicated in the development and progression of diabetic retinopathy. However, the role of AGEs in decreased levels of PEDF in the eye remains to be elucidated. In this study, we examined the effects of AGEs on PEDF gene expression in microvascular endothelial cells (ECs). Various types of immunochemically distinct AGEs, which were prepared in vitro by incubating bovine serum albumin with glucose, glyceraldehyde or glycolaldehyde, significantly decreased endothelial mRNA levels of PEDF. Furthermore, H2O2 dose-dependently suppressed PEDF gene expression in ECs. Our present results suggest that AGEs could down-regulate mRNA levels of PEDF in ECs, probably via oxidative stress generation. The deleterious effects of AGEs on diabetic retinopathy could be due, at least in part, to their PEDF-inhibitory properties.

Original languageEnglish
Pages (from-to)227-232
Number of pages6
JournalDrugs under Experimental and Clinical Research
Volume31
Issue number5-6
Publication statusPublished - 2005
Externally publishedYes

Fingerprint

Advanced Glycosylation End Products
Endothelial Cells
Gene Expression
Diabetic Retinopathy
Glyceraldehyde
Messenger RNA
pigment epithelium-derived factor
Bovine Serum Albumin
Retina
Oxidative Stress
Down-Regulation
Glucose

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology (medical)
  • Pharmacology
  • Drug Discovery

Cite this

@article{23df54a3e40e4030860413f1a174fb22,
title = "Inhibition by advanced glycation end products (AGEs) of pigment epithelium-derived factor (PEDF) gene expression in microvascular endothelial cells",
abstract = "Pigment epithelium-derived factor (PEDF) is a natural extracellular component of the retina with neuronal differentiating activity. Recently, decreased levels of PEDF in the mammalian eye have been shown to participate in the pathogenesis of diabetic retinopathy. In addition, advanced glycation end products (AGEs), senescent macroprotein derivatives that form at an accelerated rate under diabetes, have also been implicated in the development and progression of diabetic retinopathy. However, the role of AGEs in decreased levels of PEDF in the eye remains to be elucidated. In this study, we examined the effects of AGEs on PEDF gene expression in microvascular endothelial cells (ECs). Various types of immunochemically distinct AGEs, which were prepared in vitro by incubating bovine serum albumin with glucose, glyceraldehyde or glycolaldehyde, significantly decreased endothelial mRNA levels of PEDF. Furthermore, H2O2 dose-dependently suppressed PEDF gene expression in ECs. Our present results suggest that AGEs could down-regulate mRNA levels of PEDF in ECs, probably via oxidative stress generation. The deleterious effects of AGEs on diabetic retinopathy could be due, at least in part, to their PEDF-inhibitory properties.",
author = "S. Yamagishi and T. Matsui and Hiroyoshi Inoue",
year = "2005",
language = "English",
volume = "31",
pages = "227--232",
journal = "Drugs under Experimental and Clinical Research",
issn = "0378-6501",
publisher = "Bioscience Ediprint Inc.",
number = "5-6",

}

TY - JOUR

T1 - Inhibition by advanced glycation end products (AGEs) of pigment epithelium-derived factor (PEDF) gene expression in microvascular endothelial cells

AU - Yamagishi, S.

AU - Matsui, T.

AU - Inoue, Hiroyoshi

PY - 2005

Y1 - 2005

N2 - Pigment epithelium-derived factor (PEDF) is a natural extracellular component of the retina with neuronal differentiating activity. Recently, decreased levels of PEDF in the mammalian eye have been shown to participate in the pathogenesis of diabetic retinopathy. In addition, advanced glycation end products (AGEs), senescent macroprotein derivatives that form at an accelerated rate under diabetes, have also been implicated in the development and progression of diabetic retinopathy. However, the role of AGEs in decreased levels of PEDF in the eye remains to be elucidated. In this study, we examined the effects of AGEs on PEDF gene expression in microvascular endothelial cells (ECs). Various types of immunochemically distinct AGEs, which were prepared in vitro by incubating bovine serum albumin with glucose, glyceraldehyde or glycolaldehyde, significantly decreased endothelial mRNA levels of PEDF. Furthermore, H2O2 dose-dependently suppressed PEDF gene expression in ECs. Our present results suggest that AGEs could down-regulate mRNA levels of PEDF in ECs, probably via oxidative stress generation. The deleterious effects of AGEs on diabetic retinopathy could be due, at least in part, to their PEDF-inhibitory properties.

AB - Pigment epithelium-derived factor (PEDF) is a natural extracellular component of the retina with neuronal differentiating activity. Recently, decreased levels of PEDF in the mammalian eye have been shown to participate in the pathogenesis of diabetic retinopathy. In addition, advanced glycation end products (AGEs), senescent macroprotein derivatives that form at an accelerated rate under diabetes, have also been implicated in the development and progression of diabetic retinopathy. However, the role of AGEs in decreased levels of PEDF in the eye remains to be elucidated. In this study, we examined the effects of AGEs on PEDF gene expression in microvascular endothelial cells (ECs). Various types of immunochemically distinct AGEs, which were prepared in vitro by incubating bovine serum albumin with glucose, glyceraldehyde or glycolaldehyde, significantly decreased endothelial mRNA levels of PEDF. Furthermore, H2O2 dose-dependently suppressed PEDF gene expression in ECs. Our present results suggest that AGEs could down-regulate mRNA levels of PEDF in ECs, probably via oxidative stress generation. The deleterious effects of AGEs on diabetic retinopathy could be due, at least in part, to their PEDF-inhibitory properties.

UR - http://www.scopus.com/inward/record.url?scp=30144438177&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=30144438177&partnerID=8YFLogxK

M3 - Article

C2 - 16425980

AN - SCOPUS:30144438177

VL - 31

SP - 227

EP - 232

JO - Drugs under Experimental and Clinical Research

JF - Drugs under Experimental and Clinical Research

SN - 0378-6501

IS - 5-6

ER -