斯克里普斯研究所Ardem Patapoutian课题组取得一项新突破。他们探明了肾PIEZO2是肾素的重要调节因子。相关论文于2025年12月4日发表于国际顶尖学术期刊《细胞》杂志上。

课题组人员发现肾素谱系细胞中强制门控非选择性阳离子通道PIEZO2的缺失通过升高肾素来失调RAAS。研究团队观察到PIEZO2在产生肾素的肾小球旁颗粒细胞中表达，并且是体内钙动力学所必需的。肾素谱系细胞中的PIEZO2缺陷驱动肾素依赖性和MAS受体依赖性肾小球高滤过，并调节急性和慢性血容量挑战期间的RAAS。总的来说，他们的研究确定了PIEZO2在体内是肾小球旁颗粒细胞钙活性和肾素的重要调节因子。

据了解，肾素的合成和释放是控制体液平衡的肾素-血管紧张素-醛固酮系统（RAAS）的限速步骤。RAAS的一个主要激活因子是肾脏内充血压力的降低，这表明肾脏机械转导与肾素之间存在联系。然而，肾脏中机械传感器的身份及其对RAAS的生理意义尚不清楚。

附：英文原文

Title: Renal PIEZO2 is an essential regulator of renin

Author: Rose Z. Hill, Jonathan W. Nelson, Georgina Gyarmati, Silvia Medrano, Sepenta Shirvan, James A. McCormick, Sebastian Burquez, Jeanine Ahmed, Diana G. Eng, Jan Wysocki, Adrienne E. Dubin, M. Rocio Servin-Vences, Arjun Lakshmanan, R. Ariel Gomez, Maria Luisa S. Sequeira-Lopez, Stuart J. Shankland, Daniel Batlle, Jeffrey H. Miner, Janos Peti-Peterdi, Ardem Patapoutian

Issue&Volume: 2025-12-04

Abstract: Renin synthesis and release is the rate-limiting step of the renin-angiotensin-aldosterone system (RAAS) that controls fluid homeostasis. A major activator of the RAAS is a decrease in perfusion pressure within the kidneys, suggesting a link between renal mechanotransduction and renin. However, the identity of the mechanosensor(s) in the kidneys and their physiological significance to the RAAS remain unclear. We find that loss of the force-gated nonselective cation channel PIEZO2 in cells of renin lineage dysregulates the RAAS by elevating renin. We observe that PIEZO2 is expressed in renin-producing juxtaglomerular granular cells and is required for their calcium dynamics in vivo. PIEZO2 deficiency in cells of renin lineage drives renin-dependent and MAS-receptor-dependent glomerular hyperfiltration and regulates the RAAS during acute and chronic blood volume challenges. Collectively, our study identifies PIEZO2 as an essential regulator of juxtaglomerular granular cell calcium activity and renin in vivo.

DOI: 10.1016/j.cell.2025.11.013

Source: https://www.cell.com/cell/abstract/S0092-8674(25)01309-1