北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 北京大学第一临床医学院  > 肾脏内科  > 期刊论文
学科主题: 临床医学
题名:
Binding capacity and pathophysiological effects of IgA1 from patients with IgA nephropathy on human glomerular mesangial cells
作者: Wang, Y; Zhao, MH; Zhang, YK; Li, XM; Wang, HY
关键词: IgA1 ; mesangial cell ; IgA nephropathy ; pathogenesis
刊名: CLINICAL AND EXPERIMENTAL IMMUNOLOGY
发表日期: 2004-04-01
DOI: 10.1111/j.1365-2249.2004.02408.x
卷: 136, 期:1, 页:168-175
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Immunology
研究领域[WOS]: Immunology
关键词[WOS]: IMMUNOGLOBULIN-A NEPHROPATHY ; FC ALPHA RECEPTORS ; TERM-FOLLOW-UP ; NATURAL-HISTORY ; RENAL-DISEASES ; UNITED-STATES ; RAT ; GLOMERULONEPHRITIS ; WORLDWIDE ; SERUM
英文摘要:

IgA deposition in glomerular mesangium and the interaction with mesangial cells may well be the final common pathway to IgA nephropathy (IgAN). Altered hinge-region O-glycosylation of IgA1 from patients with IgAN may predispose to mesangial deposition and activation of the mesangial cell (MC) by IgA1, via a novel IgA1 receptor, and may be a key event in the pathogensis of IgAN. The aim of this study was to investigate the binding capacity and biological effects of IgA1, from both patients with IgAN and healthy controls, on human mesangial cells (HMC). Serum IgA1 was isolated with jacalin affinity chromatography, heated to aggregated form (aIgA1) and labelled with I-125. Binding capacity of aIgA1 in vitro to cultured primary HMC was evaluated by a radioligand binding assay and the specificity of binding was determined by a competitive inhibition assay. Intracellular calcium release was studied by confocal analysis and phosphorylation of extracellular signal-regulated kinase (ERK) was determined by Western blot analysis. Change of cell cycles was demonstrated by flow cytometry and HMC proliferation was evaluated by direct cell count. Expression of TGF-beta mRNA and production of supernatant fibronectin were tested by RT-PCR and indirect competitive ELISA, respectively. aIgA1 from both the patients with IgAN and normal controls bound to HMC in a dose-dependent, saturable manner, and was saturated at approximately 500 pmoles per 0.5 ml of aIgA1. aIgA1 from patients with IgAN, however, bound to HMC at a higher speed and Scatchard analysis revealed a Kd of (8.89 +/- 2.1) x 10(-8)M versus (4.3 +/- 1.2) x 10(-7)M for aIgA1 from healthy controls (P = 0.026).The binding was specific because it was only inhibited by unlabelled Mono-IgA1 (mIgA1) and not by serum albumin or IgG. aIgA1 from patients with IgAN could induce release of intracellular calcium, phosphorylation of ERK, DNA synthesis, proliferation of HMC, expression of TGF-betamRNA and secretion of fibronectin in HMC in a similar time-dependent manner as aIgA1 from healthy controls, but the effects were much stronger and the durations were much longer (P < 0.05, respectively). We conclude that aIgA1 from patients with IgAN has a higher binding capacity to HMC and stronger biological effects than aIgA1 from healthy controls. This suggests that direct interaction between IgA1 and HMC and subsequential pathophysiological responses may play an important role in the pathogenesis for IgAN.

语种: 英语
WOS记录号: WOS:000220306300023
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58802
Appears in Collections:北京大学第一临床医学院_肾脏内科_期刊论文

Files in This Item:

There are no files associated with this item.


作者单位: 1.Peking Univ, Hosp 1, Div Renal, Beijing 100034, Peoples R China
2.Peking Univ, Hosp 1, Inst Nephrol, Beijing 100034, Peoples R China

Recommended Citation:
Wang, Y,Zhao, MH,Zhang, YK,et al. Binding capacity and pathophysiological effects of IgA1 from patients with IgA nephropathy on human glomerular mesangial cells[J]. CLINICAL AND EXPERIMENTAL IMMUNOLOGY,2004,136(1):168-175.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Wang, Y]'s Articles
[Zhao, MH]'s Articles
[Zhang, YK]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Wang, Y]‘s Articles
[Zhao, MH]‘s Articles
[Zhang, YK]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace