Regulation of renal calcium transporter expressions and phosphate metabolism

肾钙转运蛋白表达和磷酸盐代谢的调节

• 批准号: 23790950
• 负责人: YATABE Midori
• 金额: $ 1.33万
• 依托单位: Fukushima Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23790950/
• 关键词: 高血圧学; カルシウム・リン代謝; 腎臓; 尿細管; カルシウム輸送体; リン; 発現調節; 食塩; カルシウム; 再吸収; Na+/Ca2+交換輸送体

Dietary NaCl intake increases the excretion of calcium into urine, which may lead to osteoporosis and urinary tract stone formation. In dietary NaCl-loaded rats, we have found that the expression of calcium reabsorbing molecules on the distal tubule increases while the protein expression of a molecule that enhances calcium reabsorption in the proximal tubule, claudin 2, is decreased. NaCl ingestion may lead to calcium loss in part via reduced expression of claudin 2. In the kidney, Na+/Ca2+exchanger 1 (NCX1) is mainly expressed in the distal tubule and the vascular smooth muscle. In vivo renal cortical administration of NCX1 inhibitor in rats lead to a decrease in serum phosphate without altering calcium dynamics, and it also decreased urinary protein and glomerular size. These observations suggest a role of renal NCX1 in phosphate metabolism and control of urinary protein and intraglomerular pressure, which are important aspects of chronic kidney disease.

饮食中氯化钠的摄入会增加尿液中钙的排泄，这可能导致骨质疏松和尿路结石形成。在饮食中添加氯化钠的大鼠中，我们发现远端肾小管中钙重吸收分子的表达增加，而近端肾小管中增强钙重吸收的分子 Claudin 2 的蛋白表达降低。氯化钠摄入可能会导致钙流失，部分原因是紧密蛋白 2 的表达减少。在肾脏中，Na+/Ca2+交换器 1 (NCX1) 主要在远端肾小管和血管平滑肌中表达。大鼠肾皮质体内给予 NCX1 抑制剂可导致血清磷酸盐降低，但不改变钙动态，并且还降低尿蛋白和肾小球大小。这些观察结果表明肾脏 NCX1 在磷酸盐代谢以及尿蛋白和肾小球内压力的控制中发挥作用，这些都是慢性肾脏疾病的重要方面。

项目成果

Renal Sodium/Calcium Exchanger 1 Inhibitor Treatment Attenuates Proteinuria and Reduces Serum Phosphate Concentration in Uninephrectomized Wistar-Kyoto Rats

肾钠/钙交换器 1 抑制剂治疗可减轻未切除肾的 Wistar-Kyoto 大鼠的蛋白尿并降低血清磷酸盐浓度

• 发表时间: 2011
• 作者: Midori Sasaki Yatabe;Junichi Yatabe;Hironobu Sanada;Junko Kimura;Tsuyoshi Watanabe
• 通讯作者: Tsuyoshi Watanabe