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Enteric neuronal Piezo1 maintains mechanical and immunological homeostasis by sensing force

文献类型：期刊论文

作者Xie, Zili9,10; Rose, Lillian8; Feng, Jing7,9; Zhao, Yonghui9; Lu, Yisi8; Kane, Harry8; Hibberd, Timothy J.6; Hu, Xueming9,10; Wang, Zhen10; Zang, Kaikai9
刊名CELL
出版日期2025-05-01
卷号188期号:9页码:36
ISSN号0092-8674
DOI10.1016/j.cell.2025.02.031
通讯作者Hu, Hongzhen(hongzhen.hu@mssm.edu) ; Jackson, Ruaidhri(ruaidhri_jackson@hms.harvard.edu)
英文摘要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.
WOS关键词NERVOUS-SYSTEM ; GASTROINTESTINAL MOTILITY ; GENE-EXPRESSION ; SEROTONIN ; CHANNELS
资助项目NIH Directors New Innovators Program[DP2AI169979] ; Paul Allen Distinguished Investigator Program ; Kenneth Rainin Innovator Award ; Crohn's and Colitis of America Foundation Senior Research Award[959859] ; National Science Foundation Graduate Research Fellowship Program[DGE2140743] ; Allen Discovery Center program ; Paul G. Allen Frontiers Group advised program of the Paul G. Allen Family Foundation ; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)[DK103901] ; NIAMS[AR077183] ; National Institute on Alcohol Abuse and Alcoholism (NIAA) of the NIH[AA027065] ; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)[AR070116] ; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)[AR077007] ; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)[AR080392] ; NIDDK[DK141106] ; National Institute of Allergy and Infectious Disease (NIAID) of the NIH[AI167933] ; National Institute of Allergy and Infectious Disease (NIAID) of the NIH[AI167047] ; [DK134773]
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
语种英语
WOS记录号WOS:001485718300002
出版者CELL PRESS
源URL[http://119.78.100.183/handle/2S10ELR8/317872]  
专题中国科学院上海药物研究所
通讯作者Hu, Hongzhen; Jackson, Ruaidhri
作者单位1.Icahn Sch Med Mt Sinai, Nash Family Dept Neurosci, New York, NY 10029 USA
2.Allen Discovery Ctr Neuroimmune Interact, New York, NY 10029 USA
3.Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA
4.Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA
5.Maynooth Univ, Kathleen Lonsdale Inst Human Hlth Res, Maynooth, Ireland
6.Flinders Univ S Australia, Coll Med & Publ Hlth, Visceral Neurophysiol Lab, Adelaide, SA, Australia
7.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Neurol & Psychiat Res & Drug Discovery, Beijing, Peoples R China
8.Harvard Med Sch, Dept Immunol, Boston, MA 02115 USA
9.Washington Univ, Sch Med, Ctr Study Itch & Sensory Disorders, Dept Anesthesiol, St Louis, MO 63110 USA
10.Icahn Sch Med Mt Sinai, Mark Lebwohl Ctr Neuroinflammat & Sensat, Dept Dermatol, New York, NY 10019 USA
推荐引用方式
GB/T 7714		 Xie, Zili,Rose, Lillian,Feng, Jing,et al. Enteric neuronal Piezo1 maintains mechanical and immunological homeostasis by sensing force[J]. CELL,2025,188(9):36.
APA Xie, Zili.,Rose, Lillian.,Feng, Jing.,Zhao, Yonghui.,Lu, Yisi.,...&Jackson, Ruaidhri.(2025).Enteric neuronal Piezo1 maintains mechanical and immunological homeostasis by sensing force.CELL,188(9),36.
MLA Xie, Zili,et al."Enteric neuronal Piezo1 maintains mechanical and immunological homeostasis by sensing force".CELL 188.9(2025):36.

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来源：上海药物研究所

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