Analysis of Molecular Mechanisms of Podocyte Injury and Its Prevention

足细胞损伤的分子机制分析及预防

• 批准号: 21591019
• 负责人: HIROMURA Keiju
• 金额: $ 2.91万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591019/
• 关键词: 足細胞; ネフローゼ症候群; 蛋白尿; 細胞内シグナル伝達経路; DNAメチル化; 内科; 腎臓内科; シグナル伝達; 糸球体; 糸球体上皮細胞; SIRP-α; 糖尿病性腎症; 糖尿病

We have examined the molecular mechanisms of podocyte injury and found the 3 following results. 1) Mizoribine directly inhibits puromycin aminonucleoside-induced podocyte injury through the mechanism independent from IMPDH inhibition. 2) The mice that express mutant SIRP. lacking cytoplasmic region show flatted and irregularly arranged foot processes. In addition, the mutant mice are sensitive to diabetic nephropathy, suggesting that SIRP. and its downstream signalling pathway are involved in the progression of diabetic nephropathy. 3) TGF-β1 induces DNA methylation of WT1 promoter in cultured podocytes. However, the degree of DNA methylation was modest, suggesting that the possibility of methylation of the upstream region of that we have examined or methylation of the promoter of WT1-related molecules.

我们研究了足细胞损伤的分子机制，发现了以下3个结果。1)米佐瑞滨通过独立于抑制IMPDH的机制直接抑制嘌呤霉素氨基核苷诱导的足细胞损伤。2)表达突变SIRP的小鼠。缺乏细胞质区，足突扁平，排列不规则。此外，突变小鼠对糖尿病肾病敏感，提示SIRP。其下游信号通路参与糖尿病肾病的发展。3) TGF-β1诱导培养足细胞WT1启动子DNA甲基化。然而，DNA甲基化的程度是适度的，这表明我们所研究的上游区域的甲基化或wt1相关分子的启动子甲基化的可能性。

项目成果

SIRPαシグナル経路の遮断は糖尿病性腎症を増悪させる

阻断 SIRPα 信号通路会加剧糖尿病肾病

• 发表时间: 2011
• 作者: 高橋哲史;廣村桂樹;浜谷博子;加藤麻衣;坂入徹;池内秀和;前島明人;黒岩卓;青木武生;大西浩史;的崎尚;野島美久
• 通讯作者: 野島美久

SIRPα(SHPS-1)Signaling Pathway Is Involved in Podocyte Structure and Function

SIRPα(SHPS-1)信号通路参与足细胞结构和功能

• 发表时间: 2009
• 作者: Tomioka M;Hiromura K;Takahashi S;Takeuchi S;Maeshima A;Kuroiwa T;Kaneko Y;Saito Y;Ohnishi Y;Matozaki T;Aoki T;Takata T;Nojima Y
• 通讯作者: Nojima Y

A Novel Case of Nephrotic Syndrome Caused by Immune-Mediated Severe

免疫介导的重症肾病综合征一例

• 发表时间: 2011
• 作者: Takahashi M;Hiromura K;et al
• 通讯作者: et al

Transforming Growth Factor(TGF)β11 Induced DNA Methylation of Wilms' Tumor Suppressor Gene (WT1) Promoter in Human Podocytes

转化生长因子(TGF)β11诱导人足细胞中Wilms肿瘤抑制基因(WT1)启动子的DNA甲基化

• 发表时间: 2011
• 作者: Hamatani H;Hiromura K;et al
• 通讯作者: et al

Nestin is a novel marker for renal tubulointerstitial injury in immunoglobulin A nephropathy

• DOI: 10.1111/j.1440-1797.2010.01342.x
• 发表时间: 2010-08
• 期刊: Nephrology
• 影响因子: 2.5
• 作者: M. Tomioka;K. Hiromura;T. Sakairi;Shigeru Takeuchi;A. Maeshima;Y. Kaneko;T. Kuroiwa;T. Takeuchi;Y. Nojima