Elucidation of the mechanisms underlying podocyte injury through endoplasmic reticulum stress and Development of novel therapeutic strategies for glomerular diseases

阐明内质网应激导致足细胞损伤的机制并开发肾小球疾病的新治疗策略

• 批准号: 21591020
• 负责人: WADA Takehiko
• 金额: $ 2.91万
• 依托单位: The University of Tokyo
• 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-21591020/
• 关键词: 腎臓学; 糸球体足細胞; 小胞体ストレス; 蛋白尿; アポトーシス; 分子シャペロン; 低酸素; グルコース; 虚血再灌流モデル

We investigated the implication of endoplasmic reticulum(ER) stress in the process of podocyte injury. Cultured growth-restrictive podocytes showed enhanced unfolded protein response under hypoxia, one of the metabolic stresses we tested. The apoptosis pathway associated with CHOP, which is one of the ER stress-related molecules, included a complicated network with Bcl-2-related proteins. Furthermore, we found that methylglyoxal, a carbonyl compound, directly damaged podocytes. Those results suggest that hypoxia, ER stress and carbonyl stress may have a crosstalk with each other and promote podocyte injury.

我们研究了内质网（ER）应激在足细胞损伤过程中的意义。培养的生长限制性足细胞在缺氧（我们测试的代谢应激之一）下表现出增强的未折叠蛋白反应。与内质网应激相关分子之一 CHOP 相关的细胞凋亡途径包括与 Bcl-2 相关蛋白的复杂网络。此外，我们发现甲基乙二醛（一种羰基化合物）直接损伤足细胞。这些结果表明缺氧、内质网应激和羰基应激可能相互影响并促进足细胞损伤。

项目成果

Abnormal Oxygen Metabolism and Epigenetic changes in Diabetic Kidney Disease

糖尿病肾病的氧代谢异常和表观遗传变化

• 发表时间: 2012
• 作者: Kawakami-Mori F;Fujita T;et al.;Nangaku M
• 通讯作者: Nangaku M

Mechanism of the development of renal anemia and its treatment

肾性贫血的发生机制及其治疗

• 发表时间: 2011
• 作者: Xu B;Zhang Y;Zhao Z;Yoshida Y;Magdeldin S;Fujinaka H;Ismail TA;Yaoita E;Yamamoto T;Nangaku M
• 通讯作者: Nangaku M

AKIの発症機序の概説

AKI 发病机制概述

• 发表时间: 2010
• 作者: Hosojima M;Kabasawa H;Takeyama A;Sato H;Yamamoto-Kabasawa K;Kaseda R;Narita I;Saito A;南学正臣
• 通讯作者: 南学正臣

腎疾患における糸球体上皮細胞傷害の意義

肾小球上皮细胞损伤在肾脏疾病中的意义

• 发表时间: 2010
• 作者: Okamoto I;Doi T;Ohtsu A;Miyazaki M;Tsuya A;Kurei K;Kobayashi K;Nakagawa K;和田健彦
• 通讯作者: 和田健彦

Glyoxalase I overexpression ameliorates renal ischemia-reperfusion injury in rats

• DOI: 10.1152/ajprenal.90575.2008
• 发表时间: 2009-04-01
• 期刊: AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
• 影响因子: 4.2
• 作者: Kumagai, Takanori;Nangaku, Masaomi;Inagi, Reiko
• 通讯作者: Inagi, Reiko