Investigation on the Role of ROS in Integrin-Mediated Signaling of Progressive Glomerulonephritis

ROS 在整合素介导的进行性肾小球肾炎信号传导中的作用研究

• 批准号: 18591189
• 负责人: KAGAMI Shoji
• 金额: $ 2.36万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591189/
• 关键词: ILK; Integrin; Parietal epithelial cell; ROS; NAD(P)H oxidase; rescent cell; Glomerulosclerosis; Renal failure

In order to clarify the role of ROS in the integrin-dependent signaling involved in progressive glomerulonephritis (GN), we investigated the localization and function of NAD(P)H oxidase -derived ROS signaling using a model of experimental GN (WKY masugi GN) and cultured parietal epithelial cells(PEC). Glomerular and crescent expression of NAD(P)H and DHE was increased in parallel with PEC proliferation and matrix accumulation during the course of GN. Inhibition of ROS production with angiotensin receptor inhibitor (ARB) in this GN model revealed that NAD(P)H oxidase-derived ROS signaling play an important role in PEC proliferation, matrix remodeling and crescent formation in progressive GN. Immunofluorescent study with cultured PEC showed that other Nox proteins except Nox2 may play a role in NAD(P)H oxidase oxidase-derived ROS signaling seen in progressive GN and crescent formation. These results indicate that NAD(P)H oxidase-derived ROS signaling play a critical role in crescent formation in progressive GN. Further study is required for development of pharmacological tool to inhibit NAD(P)H oxidase-derived ROS signaling involved in progression of GN in human.

为了阐明活性氧在进行性肾小球肾炎（GN）中的作用，我们利用实验性GN（WKY masugi GN）模型和培养的壁上皮细胞（PEC）研究了NAD（P）H氧化酶衍生的活性氧信号的定位和功能。肾小球和新月体中NAD（P）H和DHE的表达与肾小球肾炎过程中PEC增殖和基质积累平行增加。血管紧张素受体抑制剂（ARB）抑制ROS的产生在这个GN模型中显示，NAD（P）H氧化酶衍生的ROS信号在进行性GN的PEC增殖，基质重塑和新月体形成中起重要作用。免疫荧光研究表明，其他的Nox蛋白，除了Nox2可能发挥作用的NAD（P）H氧化酶氧化酶衍生的活性氧信号中看到进行性GN和新月体的形成。这些结果表明，NAD（P）H氧化酶衍生的ROS信号在进行性GN的新月体形成中起关键作用。需要进一步研究开发药理学工具来抑制NAD（P）H氧化酶衍生的ROS信号转导，该信号转导参与人类GN的进展。

项目成果

Glomerular angiotensinogen protein is enhanced in pediatric IgA nephropathy

• DOI: 10.1007/s00467-008-0801-6
• 发表时间: 2008-08-01
• 期刊: PEDIATRIC NEPHROLOGY
• 影响因子: 3
• 作者: Takamatsu, Masanori;Urushihara, Maki;Kagami, Shoji
• 通讯作者: Kagami, Shoji

腎炎進行に及ぼす細胞外基質の影響

细胞外基质对肾炎进展的影响

• 发表时间: 2006
• 期刊: 医学の歩み 218・7.8
• 作者: Takamatsu;Masanori;et. al.;漆原 真樹;Izawa Yuki;香美 祥二
• 通讯作者: 香美 祥二

Up-regulation of integrin-linked kinase activity in rat mesangio-proliferative glomerulonephritis.

大鼠系膜增生性肾小球肾炎中整合素相关激酶活性的上调。

• 发表时间: 2006
• 期刊: Life Sci 78・16
• 作者: Takamatsu;Masanori;et. al.;漆原 真樹;Izawa Yuki;香美 祥二;Shimizu Maki;Kondo Shuji;Kagami Shoji
• 通讯作者: Kagami Shoji

Big Mitogen-Activated Protein Kinase 1 (BMK1)/Extracellular Signal Regulated Kinase 5 (ERK5) Is Involved in Platelet-Derived Growth Factor (PDGF)−Induced Vascular Smooth Muscle Cell Migration

• DOI: 10.1291/hypres.30.1107
• 发表时间: 2007-11
• 期刊: Hypertension Research
• 影响因子: 5.4
• 作者: Yuki Izawa;M. Yoshizumi;K. Ishizawa;Y. Fujita;Shuji Kondo;S. Kagami;K. Kawazoe;K. Tsuchiya;S. Tomita;T. Tamaki

腎病態生理におけるERKシグナルの制御機構と役割

ERK信号在肾脏病理生理学中的控制机制和作用

• 发表时间: 2007
• 期刊: 日本小児腎臓病学会雑誌 20
• 作者: Takamatsu;Masanori;et. al.;漆原 真樹
• 通讯作者: 漆原 真樹