Development of Specific Biomarker and Molecular Targeting Therapy for Diabetic Nephropathy by RAS-independent Pathway

通过RAS非依赖性途径开发糖尿病肾病特异性生物标志物和分子靶向治疗

• 批准号: 22390169
• 负责人: DOI Toshio
• 金额: $ 12.48万
• 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 (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22390169/
• 关键词: BMP4; 糖尿病性腎症; Smad1; Sox9; バイオマーカー; 抗体医療; BMP; ALK3/6; 分子標的治療

BMP4 directly regulated Smad1 signaling in vitro. Both BMP4 and phosphorylated Smad1 were expressed in association with mesangial matrix hyperplasia in diabetic kidney. BMP4 knock-in transgenic mice showed typical mesangial matrix increase as well as BMP4 expression after induction by tamoxifen. On the other hand, BMP4 knock-out (BMP4(+/-)) mice showed amelioration of glomerular matrix hyperplasia induced by streptozotocin. Furthermore, neutralizing antibody for BMP4 normalized glomerular matrix hyperplasia and phosphorylated Smad1 expression in glomeruli of diabetic mice. These results suggest that BMP4/Smad1 signaling plays the critical pathogenetic role for diabetic nephropathy.

BMP 4在体外直接调节Smad 1信号。BMP 4和磷酸化Smad 1的表达与糖尿病肾病系膜基质增生有关。BMP-4基因敲入转基因小鼠经他莫昔芬诱导后表现出典型的系膜基质增加和BMP-4表达。另一方面，BMP 4基因敲除（BMP 4（+/-））小鼠表现出链脲佐菌素诱导的肾小球基质增生的改善。此外，BMP 4中和抗体使糖尿病小鼠肾小球中肾小球基质增生和磷酸化Smad 1表达正常化。提示BMP 4/Smad 1信号通路在糖尿病肾病的发病机制中起重要作用。

项目成果

BMP4・Smad1シグナルと糖尿病性腎症

BMP4/Smad1 信号与糖尿病肾病

• 发表时间: 2011
• 期刊: 日本腎臓学会誌
• 作者: 安部秀斉、冨永辰也;松原雄;土井俊夫
• 通讯作者: 土井俊夫

Overexpression of Smad1 Causes Remarkable Glomerulosclerosis in Diabetic Mice

Smad1 过度表达导致糖尿病小鼠出现显着的肾小球硬化

• 发表时间: 2010
• 作者: Takeshi Matsubara;Hideharu Abe;Otoya Ueda;Kou-ichi Jishage;Akira Mima;Chisato Goto;Tatsuya Tominaga;Makoto Araki;Kazuo Torikoshi;Kojiro Nagai;Noriyuki Iehara;Atsushi Fukatsu;Naoshi Fukushima;Hidenori Arai;Toshio Doi
• 通讯作者: Toshio Doi

糖尿病性腎症に関わる新たな治療標的分子の検討

糖尿病肾病相关新治疗靶分子的研究

• 发表时间: 2010
• 作者: 松原雄;安部秀斉;他
• 通讯作者: 他

BMP4 regulates podocyte injury in the diabetic nephropathy

BMP4调节糖尿病肾病足细胞损伤

• 发表时间: 2012
• 作者: Araoka T;Abe H;Tominaga T;Mima A;Matsubara T;Murakami T;Kishi S;Nagai K;Doi T;Daiju Fukuda;Tominaga T. et al.
• 通讯作者: Tominaga T. et al.

Mixed Connective Tissue Disease Developing into MPO-ANCA-positive Polyangiitis

• DOI: 10.2169/internalmedicine.50.3958
• 发表时间: 2011-01-01
• 期刊: INTERNAL MEDICINE
• 影响因子: 1.2
• 作者: Murakami, Taichi;Endo, Shuichiro;Matsumoto, Yoshihiro
• 通讯作者: Matsumoto, Yoshihiro