免疫学系Ruaidhrí Jackson研究团队的一项最新研究揭示了肠神经元Piezo1通过感应力维持机械和免疫稳态。该研究于2025年3月24日发表于国际一流学术期刊《细胞》杂志上。
在此，课题组建立了机械传感器Piezo1在胆碱能肠神经元中功能表达。光基因刺激Piezo1+胆碱能肠神经元可促进结肠运动，而Piezo1缺乏可降低胆碱能神经元的活性，减缓肠蠕动。此外，胆碱能肠神经元Piezo1缺乏可消除运动引起的胃肠运动加速。最后，该课题组发现肠神经元Piezo1功能是结肠炎运动改变所必需的，并可防止异常炎症和组织损伤。这项工作揭示了ENS是如何感知和响应机械力的。
据介绍，胃肠道（GI）在协调消化和屏障免疫时经历了无数的机械力。肠神经系统（ENS）是这些过程的中心传导体，它检测腔压来调节蠕动，而不依赖于来自中枢和外周神经系统的外来输入。然而，位于胃肠道的约5亿个肠道神经元如何感知和响应力仍然未知。
附：英文原文
Title: Enteric neuronal Piezo1 maintains mechanical and immunological homeostasis by sensing force
Author: Zili Xie, Lillian Rose, Jing Feng, Yonghui Zhao, Yisi Lu, Harry Kane, Timothy J. Hibberd, Xueming Hu, Zhen Wang, Kaikai Zang, Xingliang Yang, Quentin Richardson, Rahmeh Othman, Olivia Venezia, Ademi Zhakyp, Fang Gao, Nobuya Abe, Keren Vigeland, Hongshen Wang, Camren Branch, Coco Duizer, Liwen Deng, Xia Meng, Lydia Zamidar, Max Hauptschein, Ronan Bergin, Xinzhong Dong, Issac M. Chiu, Brian S. Kim, Nick J. Spencer, Hongzhen Hu, Ruaidhrí Jackson
Issue&Volume: 2025-03-24
Abstract: The gastrointestinal (GI) tract experiences a myriad of mechanical forces while orchestrating digestion and barrier immunity. A central conductor of these processes, the enteric nervous system (ENS), detects luminal pressure to regulate peristalsis independently of extrinsic input from the central and peripheral nervous systems. However, how the ～500 million enteric neurons that reside in the GI tract sense and respond to force remains unknown. Herein, we establish that the mechanosensor Piezo1 is functionally expressed in cholinergic enteric neurons. Optogenetic stimulation of Piezo1+ cholinergic enteric neurons drives colonic motility, while Piezo1 deficiency reduces cholinergic neuronal activity and slows peristalsis. Additionally, Piezo1 deficiency in cholinergic enteric neurons abolishes exercise-induced acceleration of GI motility. Finally, we uncover that enteric neuronal Piezo1 function is required for motility alterations in colitis and acts to prevent aberrant inflammation and tissue damage. This work uncovers how the ENS senses and responds to mechanical force.
DOI: 10.1016/j.cell.2025.02.031
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00258-2