Yamagishi S, Matsui T, Inoue H
Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
Drugs Exp Clin Res. 2005;31(5-6):227-32.
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.
色素上皮衍生因子（PEDF）是视网膜的一种天然细胞外成分，具有神经元分化活性。最近研究表明，哺乳动物眼中PEDF水平降低参与了糖尿病视网膜病变的发病机制。此外，晚期糖基化终产物（AGEs）是在糖尿病状态下加速形成的衰老大分子蛋白衍生物，也与糖尿病视网膜病变的发生和发展有关。然而，AGEs在眼部PEDF水平降低中所起的作用仍有待阐明。在本研究中，我们检测了AGEs对微血管内皮细胞（ECs）中PEDF基因表达的影响。通过将牛血清白蛋白与葡萄糖、甘油醛或乙醇醛体外孵育制备的各种免疫化学性质不同的AGEs，均显著降低了内皮细胞中PEDF的mRNA水平。此外，过氧化氢（H2O2）剂量依赖性地抑制了内皮细胞中PEDF基因的表达。我们目前的研究结果表明，AGEs可能通过产生氧化应激来下调内皮细胞中PEDF的mRNA水平。AGEs对糖尿病视网膜病变的有害作用可能至少部分归因于其抑制PEDF的特性。
