Tubular and interstitial proteases as regulators of the epithelial sodium channel (ENaC) (A04)

管状和间质蛋白酶作为上皮钠通道 (ENaC) 的调节剂 (A04)

• 批准号: 415808342
• 金额: --
• 依托单位: Institut für Zelluläre und Molekulare Physiologie
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/415808342?language=en
• 关键词: Tubular; interstitial; proteases; regulators; epithelial

The appropriate regulation of the epithelial sodium channel (ENaC) in the distal nephron is essential for the fine-tuning of renal sodium excretion. In addition to tubular proteases activating ENaC by proteolytic channel cleavage, interstitial proteases may modulate ENaC activity by activating the basolateral protease-activated receptor type 2 (PAR2). This project combines electrophysiological and molecular biological methods to identify tubular proteases relevant for proteolytic ENaC activation and to investigate the molecular mechanisms involved. Moreover, the underlying mechanisms and signaling pathways of PAR2-mediated ENaC regulation by interstitial proteases will be elucidated.

适当调节远端肾单位上皮钠通道(ENaC)对于微调肾脏钠排泄是至关重要的。除了管状蛋白水解酶通过切割蛋白通道激活ENaC外，间质蛋白水解酶还可以通过激活基底外侧蛋白水解酶激活的受体2(PAR2)来调节ENaC的活性。本项目结合电生理学和分子生物学方法，鉴定与蛋白水解性ENaC激活相关的管状蛋白水解酶，并研究其分子机制。此外，PAR2介导的间质蛋白水解酶调节ENaC的潜在机制和信号通路也将被阐明。