美国南加州大学Young-Kwon Hong课题组发现，Piezo1可调节脑膜淋巴管引流并缓解CSF过度积累。这一研究成果于2024年3月25日在线发表在国际学术期刊《自然—神经科学》上。

研究人员表示，Piezo1通过将流体流动产生的机械信号转化为生物过程来调节血管系统的多个方面。研究人员发现Piezo1是脑膜淋巴管正常发育和功能所必需的，而且通过转基因过表达或用化学激动剂Yoda1处理来激活Piezo1，足以通过改善淋巴吸收和运输来增加脑脊液（CSF）的流出。CSF的异常积聚通常会导致脑积水和脑室扩大，目前缺乏有效的治疗方法。

研究人员发现，唐氏综合征小鼠模型的脑膜淋巴管发育不全且形成异常。在患有脑积水或唐氏综合征的小鼠淋巴管中，选择性过表达Piezo1或全身给药Yoda1可显著减少病理CSF积聚、脑室扩大和其他相关疾病症状。

总之，该研究强调了Piezo1介导的淋巴机械传导在维持脑液引流中的重要性，并将Piezo1确定为治疗CSF过度积聚和脑室扩大的有望治疗靶点。

附：英文原文

Title: Piezo1 regulates meningeal lymphatic vessel drainage and alleviates excessive CSF accumulation

Author: Choi, Dongwon, Park, Eunkyung, Choi, Joshua, Lu, Renhao, Yu, Jin Suh, Kim, Chiyoon, Zhao, Luping, Yu, James, Nakashima, Brandon, Lee, Sunju, Singhal, Dhruv, Scallan, Joshua P., Zhou, Bin, Koh, Chester J., Lee, Esak, Hong, Young-Kwon

Issue&Volume: 2024-03-25

Abstract: Piezo1 regulates multiple aspects of the vascular system by converting mechanical signals generated by fluid flow into biological processes. Here, we find that Piezo1 is necessary for the proper development and function of meningeal lymphatic vessels and that activating Piezo1 through transgenic overexpression or treatment with the chemical agonist Yoda1 is sufficient to increase cerebrospinal fluid (CSF) outflow by improving lymphatic absorption and transport. The abnormal accumulation of CSF, which often leads to hydrocephalus and ventriculomegaly, currently lacks effective treatments. We discovered that meningeal lymphatics in mouse models of Down syndrome were incompletely developed and abnormally formed. Selective overexpression of Piezo1 in lymphatics or systemic administration of Yoda1 in mice with hydrocephalus or Down syndrome resulted in a notable decrease in pathological CSF accumulation, ventricular enlargement and other associated disease symptoms. Together, our study highlights the importance of Piezo1-mediated lymphatic mechanotransduction in maintaining brain fluid drainage and identifies Piezo1 as a promising therapeutic target for treating excessive CSF accumulation and ventricular enlargement.

DOI: 10.1038/s41593-024-01604-8

Source: https://www.nature.com/articles/s41593-024-01604-8