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Binding capacity and pathophysiological effects of IgA1 from patients with IgA nephropathy on human glomerular mesangial cells
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
2004-04-01
DOI10.1111/j.1365-2249.2004.02408.x
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
引用统计
被引频次:45[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/58802
专题北京大学第一临床医学院_肾脏内科
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
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GB/T 7714
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.
APA Wang, Y,Zhao, MH,Zhang, YK,Li, XM,&Wang, HY.(2004).Binding capacity and pathophysiological effects of IgA1 from patients with IgA nephropathy on human glomerular mesangial cells.CLINICAL AND EXPERIMENTAL IMMUNOLOGY,136(1),168-175.
MLA Wang, Y,et al."Binding capacity and pathophysiological effects of IgA1 from patients with IgA nephropathy on human glomerular mesangial cells".CLINICAL AND EXPERIMENTAL IMMUNOLOGY 136.1(2004):168-175.
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