Novel strategy to regulate renal channels and transporters

调节肾通道和转运蛋白的新策略

• 批准号: 22249032
• 负责人: SASAKI SEI
• 金额: $ 30.2万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-22249032/
• 关键词: 水・電解質代謝学; 塩分感受性高血圧; 遺伝子改変マウス; アクアポリン; 膜輸送体; 腎臓; ケミカルライブラリー; 輸送体; リン酸化; 水チャネル; 高血圧; AQP2; WNKキナーゼ; アンギオテンシンII; SPAK

The purpose of our study was to clarify novel regulatory mechanisms of renal transporters and channels, especially AQP water channels, CLC chloride channels, and SLC12A transporters, and to try to develop new strategy to treat diseases caused by the dysregulation of these transporters and channels. We clarified the molecular pathogenesis of renal cyst formation caused by the deletion of AQP11, identified the agents to rescue endoplasmic reticulum (ER)-retained disease-causing mutant Barttin, and isolated some chemical compounds that inhibited WNK-OSR1/SPAK-SLC12A signaling.

本研究旨在阐明肾脏转运体和通道，尤其是AQP水通道、CLC氯通道和SLC 12 A转运体的新的调控机制，并尝试开发新的策略来治疗这些转运体和通道失调引起的疾病。我们阐明了AQP 11缺失引起的肾囊肿形成的分子发病机制，鉴定了拯救内质网（ER）滞留致病突变体Barttin的药物，并分离出一些抑制WNK-OSR 1/SPAK-SLC 12 A信号传导的化合物。

项目成果

Renal phenotype of WNK3 knockout mouse

WNK3基因敲除小鼠的肾脏表型

• 发表时间: 2011
• 作者: Oi K;Sohara E;Rai T;Chiga M;Alessi DR;Sasaki S;Uchida S
• 通讯作者: Uchida S

腎臓内科学

肾脏病学

• 发表时间: 2010
• 作者: Kawai Y;Ajima K;Nagai T;Kaidoh M;Ohhashi T;佐々木成編集
• 通讯作者: 佐々木成編集

WNK3 regulates blood pressure through the regulation of vascular OSR1 / SPAK-NKCC1 phosphorylation cascade

WNK3通过调节血管OSR1/SPAK-NKCC1磷酸化级联来调节血压

• 发表时间: 2013
• 作者: Zeniya M;Sohara E;Oi K;Chiga M;Susa K;Mori T;Takahashi D;Rai T;Sasaki S;Uchida S
• 通讯作者: Uchida S

Ser-261 phosphorylation is an endocytic signal of aquaporin-2 water channel.

Ser-261 磷酸化是 aquaporin-2 水通道的内吞信号。

• 发表时间: 2013
• 作者: Yui N;Uchida S;Sasaki S.
• 通讯作者: Sasaki S.

Assessment and significance of abdominal aortic calcification in chronic kidney disease

• DOI: 10.1093/ndt/gfp728
• 发表时间: 2010-06-01
• 期刊: NEPHROLOGY DIALYSIS TRANSPLANTATION
• 影响因子: 6.1
• 作者: Hanada, Shigeru;Ando, Ryoichi;Sasaki, Sei
• 通讯作者: Sasaki, Sei