Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
Pharmacol Res. 2010 Feb;61(2):103-7. doi: 10.1016/j.phrs.2009.07.003. Epub 2009 Jul 25.
We have recently found that serum levels of pigment epithelium-derived factor (PEDF), a glycoprotein with anti-oxidative and anti-inflammatory properties, are elevated in proportion to the accumulation of the number of the components of the metabolic syndrome. Since formation and accumulation of advanced glycation end products (AGEs) progress under the metabolic syndrome and that PEDF could inhibit the AGE-elicited tissue damage, it is conceivable that PEDF levels may be increased as a counter-system against AGEs in patients with the metabolic syndrome. However, correlation between circulating levels of AGEs and PEDF in humans remains to be elucidated. In this study, we investigated the relationship between serum AGE and PEDF levels in a general population and examined the effects of AGEs on PEDF gene expression in vitro. One hundred ninety-six Japanese subjects in a general population underwent a complete history and physical examination, determination of blood chemistries, including serum levels of AGEs and PEDF. In multiple regression analyses, creatinine, body mass index, triglycerides, AGEs and insulin were independently correlated with serum PEDF levels. AGEs dose-dependently increased PEDF gene expression in cultured adipocytes and liver cells. Our present study demonstrated first that circulating AGEs were one of the independent correlates of serum levels of PEDF. Adipose tissue and liver may be target organs for the AGE-induced PEDF overexpression in humans. Serum PEDF levels may be elevated in response to circulating AGEs as a counter-system against the AGE-elicited tissue damage.
我们最近发现，色素上皮衍生因子（PEDF）的血清水平与代谢综合征成分的积累数量成正比升高，PEDF 是一种具有抗氧化和抗炎特性的糖蛋白。由于代谢综合征下的形成和积累的晚期糖基化终产物（AGEs），并且 PEDF 可以抑制 AGE 引起的组织损伤，因此可以想象，患有代谢综合征的患者体内的 PEDF 水平可能会增加作为对抗 AGE 的反系统。然而，人类循环 AGEs 和 PEDF 之间的相关性仍有待阐明。在这项研究中，我们调查了一般人群中血清 AGE 和 PEDF 水平之间的关系，并在体外检查了 AGEs 对 PEDF 基因表达的影响。一般人群中的 196 名日本受试者接受了完整的病史和体格检查，测定了包括血清 AGE 和 PEDF 水平在内的血液化学物质。在多元回归分析中，肌酐、体重指数、甘油三酯、AGEs 和胰岛素与血清 PEDF 水平独立相关。AGEs 以剂量依赖性方式增加培养的脂肪细胞和肝细胞中的 PEDF 基因表达。我们的研究首次表明，循环 AGEs 是血清 PEDF 水平的独立相关因素之一。脂肪组织和肝脏可能是人类 AGE 诱导的 PEDF 过表达的靶器官。血清 PEDF 水平可能会升高，以作为对抗 AGE 引起的组织损伤的反系统。
