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The role of receptor molecules for IgA in the pathogenic mechanism of IgA nephropathy

IgA受体分子在IgA肾病发病机制中的作用

基本信息

批准号：
16390242
负责人：
NARITA Ichiei
金额：
$ 7.1万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

The purpose of this study was to elucidate the mechanism of mesangial IgA deposition in IgA nephropathy, especially through investigating the dynamics of receptors for IgA molecules and their metabolisms. Three molecules, pIgR (polymeric immuno-globulin receptor), FcαR, and ASGPR (asyaloglycoprotein receptor), have been known as receptor molecules for IgA. In addition, fourth molecules, TfR (Transferrin receptor), has recently been identified as receptor of IgA. It has been shown that the expression of TfR is upregulated in glomeruli of patients with IgAN, suggesting that TfR plays a role in formation of pathological immune complex in this disease.In this study, we investigated the possible associations of genetic polymorphisms in these receptor molecules and IgAN. However, we did not find any significant association of FcαR, ASGPR, and TfR polymorphisms and IgAN.During the last decade, several lines of evidence have been reported indicating that incompleteness of O-glycosylation in the IgAl hinge region may be a plausible cause of the IgAl deposition. O-Glycans are found in many glycoproteins, particularly in secretory glycoproteins. The common core 1 O-glycan structure, Galb-1-3GalNAc-R, is a precursor for many extended mucin-type O-glycan structures on animal cell surfaces and secreted glycoproteins including IgAl. We also have published a review paper about this notion in Kidney International (Narita I, et al. 2007).

本研究的目的是通过对伊加分子受体及其代谢的动态研究，阐明伊加肾病系膜伊加沉积的机制。已知三种分子，pIgR（多聚免疫球蛋白受体）、FcαR和ASGPR（唾液酸糖蛋白受体）是伊加的受体分子。此外，第四种分子，TfR（转铁蛋白受体），最近被鉴定为伊加的受体。已有研究表明，IgAN患者肾小球中TfR的表达上调，提示TfR参与了IgAN病理性免疫复合物的形成，本研究探讨了这些受体分子的遗传多态性与IgAN的关系。然而，我们没有发现FcαR、ASGPR和TfR多态性与IgAN有任何显著的关联。在过去的十年中，一些证据表明IgAl铰链区O-糖基化的不完全性可能是IgAl沉积的合理原因。O-聚糖存在于许多糖蛋白中，特别是分泌性糖蛋白中。常见的核心10-聚糖结构Galb-1-3GalNAc-R是动物细胞表面上许多延伸的粘蛋白型0-聚糖结构和分泌的糖蛋白（包括IgAl）的前体。我们还在Kidney International上发表了一篇关于这一概念的综述论文（Narita I，et al. 2007）。