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PIEZO1是一种远端脏机械传感器,对于流动诱导的K+分泌物是必需的
Rolando Carrisoza-Gaytan1, Stephanie M Mutchler2, Francisco Carattino1
1Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
The Journal of clinical investigation
|March 1, 2024
概括
细胞中的机械敏感PIEZO1通道感知流体流动,触发分泌所必需的信号. 这条通道在高饮食中受到上调,对于维持平衡至关重要.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 细胞生物学 细胞生物学
- 生理学 生理学 生理学
背景情况:
- 干细胞 (ICs) 使用激活的BK通道进行流动诱导的分泌 (FIKS).
- 智能集成器检测增加的光流的精确机制尚未完全理解.
- 一个机械敏感通道PIEZO1在ICs的底侧膜中表达.
研究的目的:
- 调查PIEZO1在感知光流和调解脏ICs中的FIKS中的作用.
- 为了确定饮食摄入量是否改变了PIEZO1的表达或功能.
- 评估IC中PIEZO1缺失对平衡的生理后果.
主要方法:
- 隔离的皮层收集管道 (CCD) 用于测量细胞内 ([Ca2+]i) 和BK通道活性.
- 使用药理工具 (GsMTx4,Yoda1) 来调节机械敏感通道和PIEZO1.
- 在ICs (IC-Piezo1-KO) 中对Piezo1的条件基因删除在小鼠中进行.
- 处理在体内使用口服挑战和体积扩张进行了评估.
主要成果:
- 机械敏感通道的抑制减少了流量诱导的[Ca2+]i,而PIEZO1激活增加了[Ca2+]i和BK通道活性.
- 高的饮食增强了Yoda1依赖的[Ca2+]i在CCD中的增加.
- IC-Piezo1-KO小鼠对流动和Yoda1的[Ca2+]i反应变得,FIKS被废除.
- 雄性IC-Piezo1-KO小鼠表现出分泌受损和血水平升高.
- 在高饮食的IC-Piezo1-KO小鼠的IC中,BKα子单元的表达减少.
结论:
- PIEZO1对于调解流动诱导的进入脏ICs至关重要.
- 作为对高饮食的反应,CCD中的PIEZO1表达被上调.
- PIEZO1对于正常的FIKS是必要的,并且在调节分泌方面发挥着至关重要的作用.
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