Role of monocyte chemotactic protein-1 and nuclear factor kappa B in the pathogenesis of proliferative diabetic retinopathy
Role of monocyte chemotactic protein-1 and nuclear factor kappa B in the pathogenesis of proliferative diabetic retinopathy
复制标题
DOI：
10.1016/j.diabres.2006.04.017
复制
发表时间：
2006-12-01
影响因子：
5.1
通讯作者：
Harada, Takayuki
中科院分区：
文献类型：
--
作者：
Harada, Chikako;Okumura, Akinori;Harada, Takayuki
单核细胞趋化蛋白-1（MCP-1）的眼内浓度在增殖性糖尿病视网膜病变（PDR）中增加。核因子κ B（NF-κ B）是一种转录因子，其结合位点位于MCP-1基因启动子区。本研究旨在探讨MCP-1和NF-κ B在PDR发病机制中的潜在作用。视网膜前膜（ERM）的样品中获得的玻璃体切除术从19眼PDR和16眼特发性ERM。对它们进行处理以进行RT-PCR分析。处理4个PDR ERM用于免疫组织化学分析。此外，培养的Muller神经胶质细胞用糖化白蛋白或高糖刺激。刺激后，我们检测了NF-κ B p50的核定位、MCP-1启动子活性和培养基中MCP-1浓度。MCP-Ⅰ mRNA在PDR中的表达（74%）明显高于特发性ERMs（38%）（P < 0.05）.免疫组织化学分析显示MCP-1蛋白与活性形式的NF-κ B p50共定位。体外研究表明，糖化白蛋白或高葡萄糖诱导NF-κ B活化，随后上调MCP-1启动子活性和神经胶质细胞中的蛋白质产生。提示MCP-1在NF-κ B的调控下参与了PDR的发病过程。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
Intraocular concentrations of monocyte chemotactic protein-1 (MCP-1) are increased in proliferative diabetic retinopathy (PDR). Nuclear factor kappa B (NF-kappa B) is a transcription factor, and NF-kappa B binding site is located in gene promoter of MCP-1. This study was conducted to investigate the potential role of MCP-I and NF-kappa B in the pathogenesis of PDR. Epiretinal membrane (ERM) samples were obtained during vitrectomy from 19 eyes with PDR and 16 eyes with idiopathic ERM. They were processed for RT-PCR analysis. Four PDR ERMs were processed for immunohistochemical analysis. In addition, cultured Muller glial cells were stimulated with glycated albumin or high glucose. After the stimulation, we examined nuclear localization of NF-kappa B p50, MCP- I promoter activity, and MCP-1 concentration in culture media. MCP- I mRNA expression was significantly higher in PDR (74%) than in idiopathic ERMs (38%) (P < 0.05). Immunohistochemical analysis revealed that MCP- I protein is colocalized with active form of NF-KB p50. In vitro studies demonstrated that glycated albumin or high glucose induces NF-KB activation followed by up-regulation of MCP-I promoter activity and protein production in glial cells. These results suggest that MCP-1, under the regulation of NF-KB, is involved in the pathogenesis of PDR. (c) 2006 Elsevier Ireland Ltd. All rights reserved.