Elucidation of the pathogenic mechanism of IgA nephropathy through identification and functional analysis of the receptor for the insufficient glycosylated IgA molecules

通过糖基化IgA分子不足受体的鉴定和功能分析阐明IgA肾病的发病机制

• 批准号: 20390234
• 负责人: NARITA Ichiei
• 金额: $ 11.48万
• 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: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20390234/
• 关键词: IgA腎症; 糖鎖不全; 慢性糸球体腎炎; メサンギウム細胞; 受容体; インテグリン; コラーゲン; クローニング

IgA nephropathy is characterized by mesangial deposition of IgA1 and galactose-deficient IgA1 is assumed to play a pathogenic role. However, the identity of the receptor for IgA1 is still controversial. Hence, the aim of this study was to explore the receptor for galactose-deficient IgA1. Human monoclonal IgA1 was treated with exoglycosidase and FITC-conjugated galactose-deficient IgA1 was used as a probe to detect the receptor in cultured human mesangial cells. According to comprehensive gene expression analysis, we revealed that galactose-deficient IgA1-collagen complex formation would be proposed as one of the candidate mechanisms of IgA1 deposition and proliferative signal transduction via integrinα2/β1 heterodimer in human mesangial cells.

伊加肾病的特点是肾小球系膜沉积的IgA 1和半乳糖缺乏的IgA 1被认为是发挥致病作用。然而，IgA 1受体的身份仍有争议。因此，本研究的目的是探索半乳糖缺陷型IgA 1的受体。人单克隆IgA 1处理与外切糖苷酶和FITC标记的半乳糖缺陷型IgA 1被用作探针，以检测在培养的人系膜细胞的受体。综合基因表达分析结果，我们认为半乳糖缺陷型IgA 1-胶原复合物的形成可能是人肾小球系膜细胞中IgA 1沉积和整合素α2/β1异源二聚体介导的增殖信号转导的机制之一。

项目成果

Injured kidney cells express SM22alpha(transgelin): Unique features distinct from alpha-smooth muscle actin(alphaSMA)

受损肾细胞表达 SM22α（转凝胶蛋白）：与 α-平滑肌肌动蛋白 (αSMA) 不同的独特功能

• 发表时间: 2011
• 期刊: Nephrology(Carlton)
• 作者: Sakamaki Y;Sakatsume M;Wang X;Inomata S;Yamamoto T;Gejyo F;Narita I
• 通讯作者: Narita I

Effect of a Carbonaceous Oral Adsorbent on the Progression of CKD: A Multicenter, Randomized, Controlled Trial

• DOI: 10.1053/j.ajkd.2009.05.011
• 发表时间: 2009-09-01
• 期刊: AMERICAN JOURNAL OF KIDNEY DISEASES
• 影响因子: 13.2
• 作者: Akizawa, Tadao;Asano, Yasushi;Kurokawa, Kiyoshi
• 通讯作者: Kurokawa, Kiyoshi

Quantitative Histological Analysis of SM22 alpha(Transgelin) in an Adriamycin-Induced Focal Segmental Glomerulosclerosis Model

阿霉素诱导局灶节段性肾小球硬化模型中 SM22 α（Transgelin）的定量组织学分析

• 发表时间: 2011
• 期刊: Nephron Exp Nephrol
• 作者: Wang X;Sakatsume M;Sakamaki Y;Inomata S;Yamamoto T;Narita I
• 通讯作者: Narita I

IgA腎症の病態と治療

IgA肾病的病理学和治疗

• 发表时间: 2019
• 作者: Kadoya T;Sakakibara A;Kitayama K;Yamada Y;Higuchi S;Kawakita R;Kawasaki Y;Fujino M;Murakami Y;Shimura M;Murayama K;Ohtake A;Okazaki Y;Koga Y;Yorifuji T.;島 友子
• 通讯作者: 島 友子

Megalin is downregulated via LPS-TNF-alpha-ERK1/2 signaling pathway in proximal tubule cells

近曲小管细胞中巨蛋白通过 LPS-TNF-α-ERK1/2 信号通路下调

• DOI: 10.1016/j.bbrc.2011.02.118
• 发表时间: 2011
• 期刊: Biochem Biophys Res Commun
• 作者: Takeyama A;et al.
• 通讯作者: et al.