Study on cell-specific roles of nudear factor KB in the progression of renal diseases with genetically modified animals

核因子KB在转基因动物肾脏疾病进展中的细胞特异性作用研究

• 批准号: 18590903
• 负责人: HAYASHI Matsuhiko
• 金额: $ 2.6万
• 依托单位: Keio University
• 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-18590903/
• 关键词: NFκB; nephrotoxic serum nephritis; Cre-recombinase; Lox-P; 慢性腎臓病; loxP; transgenic mouse; Cre recombinase; tie-2; AQP7

At first, to generate mice lines in which Cre-recombinase is expressed only in adipocyte and proximal tubules S3 segment, aquaporin promoter region with Cre-recombinase expression vector was used to. We obtained 7 lines of mouse, although, Cre-recombinase activity was observed in a patchy manner in the proximal tubules S1 and S2 segments. We also examined the expression of Cre-recombinase mRNA expression in various organs and tissues. Strong expression was seen in testis and adipose tissue, while significant expression was also seen in various tissues, such as liver, muscle, and intestine. From these results, we abandoned these lines of mouse for our study.On the other hand, we have previously developed conditional transgenic mouse, in which IκBΔN, a dominant-negative form of inhibitory factor of NFκB, is expressed in the presence of Cre-recombinase. We obtained double transgenic mouse of IκBΔN conditional transgenic mouse and podocyte-specific Cre-recombinase expressing mouse. Nephrotoxic serum nephritis was induced in this double transgenic mouse and wild-type mouse. Urinary excretion of protein was significantly lower in double transgenic mouse and crescent formation and glomerular changes were less prominent in double transgenic mouse, too. Double transgenic mouse of IκBΔN conditional transgenic mouse and endothelial-cell-specific Cre-recombinase expressing mouse was not born suggesting that endothelial NFκB activity is required to survive during development.Furthermore, we examined roles of clusterin in renal tubular cell apoptosis and it was suggested that clusterin might facilitate apoptosis.From these results, it is suggested that NFκB activity in podocytes plays important roles in the pathogenesis of nephrotoxic serum nephritis.

首先，为了产生仅在脂肪细胞和代理管S3段中表达CRE成年酶的小鼠线，使用了具有CRE-成分酶表达载体的水通道蛋白启动子区域。我们获得了7条小鼠，尽管在代理管S1和S2段中以斑点的方式观察到CRE聚合酶活性。我们还检查了各种器官和组织中CRE成年酶mRNA表达的表达。从这些结果中表达强烈的表达，我们放弃了这些小鼠线进行研究。另一方面，我们先前已经开发了有条件的转基因小鼠，其中IκBΔn是NFκB的抑制性抑制因子的显性阴性形式，在存在CRE聚集酶的情况下表达。我们获得了有条件转基因小鼠的IκBΔN的双转基因小鼠和表达小鼠的足细胞特异性CRE聚合酶。在这款双转基因小鼠和野生型小鼠中诱导肾毒性血清肾炎。在双转基因小鼠中，蛋白质的极端蛋白质明显降低，新月形形成，肾小球变化在双转基因小鼠中也较不突出。 IκBΔN的双重转基因小鼠有条件转基因小鼠和表达小鼠的内皮细胞特异性CRE结构酶，这表明需要内皮NFκB活性才能在发育过程中生存。furthermore。，我们研究了簇素在肾脏结核病中的作用，并提出了IS nnf inf thef inf thef inf thef inf clusterin。足细胞在肾毒性血清肾炎的发病机理中起重要作用。

项目成果

ジフテリア毒素受容体を介した近位尿細管S3セグメント特異的除去マウスの作

通过白喉毒素受体特异性消融近端小管 S3 段的小鼠的产生

• 发表时间: 2007
• 作者: 門川 俊明;関根 美知子;多屋 長治;松岡 邦枝;吉野 純;犬飼 舞;伊藤 裕;林 松彦;鈴木 明身;米川 博道
• 通讯作者: 米川 博道

Inhibition of NF-kappaB-dependent Bc1-xL expression by clusterin promotes albumin-induced tubular cell apoptosis

簇蛋白抑制 NF-κB 依赖性 Bc1-xL 表达促进白蛋白诱导的肾小管细胞凋亡

• 发表时间: 2008
• 期刊: Kidney International 73
• 作者: Takase;O;Minto;AW;Puri;TS;Cunningham;PN;Jacob;A;Hayashi;M;Quigg;RJ
• 通讯作者: RJ

Microarray analysis of a reversible model and an irreversible model of anti-Thy-1 nephritis.

• DOI: 10.1038/sj.ki.5000191
• 发表时间: 2006-03
• 期刊: Kidney international
• 影响因子: 19.6
• 作者: M. Tsuji;T. Monkawa;J. Yoshino;M. Asai;S. Fukuda;H. Kawachi;F. Shimizu;M. Hayashi;T. Saruta

アルドステロン持続注入ラットにおけるスピロノラクトンとトリアムテレンの腎障害に対する効果の比較

螺内酯与氨苯蝶啶对醛固酮持续输注大鼠肾损伤的影响比较

• 发表时间: 2006
• 作者: 福田 誠一;門川 俊明;浅井 昌樹;林松 彦
• 通讯作者: 林松 彦

Study on renal protective effects focused on NF-kappaB of eicosapentoeic acid in LPS-induced renal tubular damage

二十碳五烯酸NF-κB对LPS所致肾小管损伤的肾保护作用研究

• 发表时间: 2007
• 作者: Takase;O;Hishikawa;K;Marumo;F;Yoshikawa;M;Hayashi;M;Richard;Q;Fujita;T
• 通讯作者: T