Mechanism of prostasin-induced aldosterone production

前列腺素诱导醛固酮产生的机制

• 批准号: 20390238
• 负责人: TOMITA Kimio
• 金额: $ 11.81万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20390238/
• 关键词: 高血圧; 腎; ナトリウム; アルドステロン; プロスタシン; セリンプロテアーゼ; プロセッシングエンザイム

The control of blood pressure (BP) and extracellular fluid volume primarily depends on renal regulation of sodium reabsorption and excretion. The epithelial sodium channel (ENaC) plays an important role in the regulation of blood pressure by modulating Na reabsorption in the kidney. We previously revealed that prostasin increased Na transport through ENaC in the co-expression system using Xenopus oocytes, and that aldosterone increased the abundance of prostasin in human and rat urine and in the cultured medium of a mouse cortical collecting duct cell line.We examine if prostasin increases the aldosterone synthesis in a human adrenocortical cell line (H295R cells). Luciferase assay using CYP11B2 promoter is used to see if the prostasin increases the transcriptional activity of CYP11B2. In addition, ENaC activity is investigated in Dahl hypertensive rats which are the model animal of salt-sensitive hypertension.

血压（BP）和细胞外液量的控制主要取决于肾脏对钠重吸收和排泄的调节。上皮钠通道 (ENaC) 通过调节肾脏中钠的重吸收，在血压调节中发挥重要作用。我们之前发现，前列腺素增加了爪蟾卵母细胞共表达系统中通过 ENaC 的 Na 转运，醛固酮增加了人和大鼠尿液以及小鼠皮质集合管细胞系培养基中前列腺素的丰度。我们检查前列腺素是否增加人肾上腺皮质细胞系（H295R 细胞）中醛固酮的合成。使用 CYP11B2 启动子的荧光素酶测定用于观察前列腺素是否增加 CYP11B2 的转录活性。此外，在 Dahl 高血压大鼠（盐敏感性高血压的模型动物）中研究了 ENaC 活性。

项目成果

Aberrant ENaC activation in Dahl salt-sensitive rats

• DOI: 10.1097/hjh.0b013e32832c7d23
• 发表时间: 2009-08-01
• 期刊: JOURNAL OF HYPERTENSION
• 影响因子: 4.9
• 作者: Kakizoe, Yutaka;Kitamura, Kenichiro;Tomita, Kimio
• 通讯作者: Tomita, Kimio

Human Sodium Phosphate Transporter 4 (hNPT4/SLC17A3) as a Common Renal Secretory Pathway for Drugs and Urate

• DOI: 10.1074/jbc.m110.121301
• 发表时间: 2010-11-05
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Jutabha, Promsuk;Anzai, Naohiko;Sakurai, Hiroyuki
• 通讯作者: Sakurai, Hiroyuki

Urinary prostasin in humans: relationships among prostasin, aldosterone and epithelial sodium channel activity

• DOI: 10.1038/hr.2009.6
• 发表时间: 2009-04-01
• 期刊: HYPERTENSION RESEARCH
• 影响因子: 5.4
• 作者: Koda, Aya;Wakida, Naoki;Kitamura, Kenichiro
• 通讯作者: Kitamura, Kenichiro

Camostat mesilate inhibits prostasin activity and reduces blood pressure and renal injury in salt-sensitive hypertension

• DOI: 10.1097/hjh.0b013e328317a762
• 发表时间: 2009-01-01
• 期刊: JOURNAL OF HYPERTENSION
• 影响因子: 4.9
• 作者: Maekawa, Ai;Kakizoe, Yutaka;Kitamura, Kenichiro
• 通讯作者: Kitamura, Kenichiro

Vasopressin and hyperosmolality regulate NKCC1 expression in rat OMCD

• DOI: 10.1038/hr.2009.52
• 发表时间: 2009-08
• 期刊: Hypertension Research
• 影响因子: 5.4
• 作者: S. Wakamatsu;H. Nonoguchi;M. Ikebe;K. Machida;Y. Izumi;Hasiyet Memetimin;Y. Nakayama;T. Nakanishi;Y. Kohda;K. Tomita