钙黏蛋白E与糖尿病肾病的相关性研究  

Relationship between E- cadherin and diabetic nephropathy

作　　者：姜洪娟[1] 柳刚[2] 迟翔宇[1] 张玄[1] 

机构地区：[1]山东大学附属省立医院保健科,济南250021 [2]山东大学第二医院肾内科

出　　处：《中华肾脏病杂志》2014年第5期351-355,共5页Chinese Journal of Nephrology

基　　金：卫生部临床学科重点项目（2010-2012）;山东省优秀中青年科学家科研奖励基金计划（BS2013YY055）;山东省医药卫生科技发展计划项目（2013WS0119）;山东省医药卫生科技发展计划（保健）项目（2013BJYB18）

摘　　要：目的应用蛋白质组学技术筛选糖尿病肾病（DN）患者尿液的相关差异蛋白，检测差异蛋白钙黏蛋白E（E-cadherin）在DN患者尿液及肾组织中的表达，以期发现新的DN相关差异蛋白。方法选择本院经肾活检确诊的1型DN（TIDN）和2型DN（T2DN）患者各12例，同时选择肾病综合征（NS）患者及健康志愿者各12例作为对照。应用2DE/MS比较蛋白质组学技术筛选DN患者及对照组人群尿中的DN相关差异蛋白。采用Western印迹法验证尿中差异蛋白的表达，免疫组织化学法检测肾组织中差异蛋白的表达。结果2DE/MS结果显示，与NS组和健康对照组相比，T1DN组和T2DN组患者有1个差异蛋白点的蛋白丰度呈异常升高，经鉴定为E-cadherin。Western印迹结果显示，与NS和健康对照组相比，TIDN和T2DN组患者尿液中E-cadherin表达明显增高（均P〈0．01）。免疫组化结果显示，E-cadherin主要表达于肾小管上皮细胞的细胞膜和细胞质，其在DN肾脏中的表达较健康对照组显著降低（P〈0．05）。结论DN患者尿液中E-cadherin蛋白特异性升高，可作为一种新的DN相关差异性蛋白。Objective To identify novel biomarker for diabetic nephropathy （DN） by urinary proteomic methods, and to detect the expression of E-cadherin in urine and renal tissue of patients with DN. Methods Urine samples were collected from 12 cases of type 1 diabetic nephropathy patients （T1DN）, 12 cases of type 2 diabetic nephropathy patients （T2DN）, 12 cases of nephritic syndrome patients （NS）, and 12 cases of healthy Controls. Comparative proteomic approach of two-dimensional gel electrophoresis （2-DE） and mass spectrometry （MS） were employed to identify DN-related biomarker in urine samples. The differential expression of the identified biomarker in urine samples and renal biopsy specimens were detected by Western blotting and immunohistochemistry method. Results E-cadherin was identified by 2DE/MS, which was significantly up-regulated in T1DN and T2DN groups （all P 〈 0.01）. Western blotting confirmed the expression of E-cadherin was significantly higher in T1DN and T2DN groups than in NS and Control groups （all P〈0.01）. Immunohistochemical stain showed E-cadherin was mainly expressed in the membrane and cytoplasm of renal tubular epithelial cell, and its expression was markedly decreased in DN kidneys compared with healthy Controls （P 〈 0.05）. Conclusions E-cadherin is identified as a novel DN-related biomarker, which is specifically increased in urine of DN patients.

关 键 词：糖尿病肾病 蛋白质组学 尿液 钙黏蛋白E 

分 类 号：R587.2[医药卫生—内分泌]