The mechanosensitive Piezo1 channel mediates heart mechano-chemo transduction.
The mechanosensitive Piezo1 channel mediates heart mechano-chemo transduction.
复制标题
机械敏感的 Piezo1 通道介导心脏机械-化学转导
DOI：
10.1038/s41467-021-21178-4
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发表时间：
2021-02-08
影响因子：
16.6
通讯作者：
Xiao B
中科院分区：
文献类型：
--
作者：
Jiang F;Yin K;Wu K;Zhang M;Wang S;Cheng H;Zhou Z;Xiao B
跳动的心脏具有使心输出量适应机械负荷变化的内在能力。有百年历史的Frank-Starling定律和Anrep效应已经证明，在舒张充盈期间拉伸心脏会增加其收缩力。然而，分子力学转导机制及其对心脏健康和疾病的影响仍然难以捉摸。在这里，我们发现机械激活的Piezo 1通道将心肌细胞的机械拉伸转化为Ca 2+和活性氧（ROS）信号，这决定了心脏的机械活动。无论是心脏特异性敲除或过表达的Piezo 1在小鼠中的结果缺陷Ca 2+和ROS信号和心肌病的发展，证明了一个稳态的作用Piezo 1。Piezo 1通过心肌细胞的自主反应在小鼠和人类患病心脏中病理性上调。因此，Piezo 1作为一个关键的心脏机械传感器启动机械-化学转导，从而维持正常的心脏功能，并可能代表一个新的治疗靶点，用于治疗人类心脏疾病。跳动的心脏通过不完全理解的机械转导机制使心输出量适应机械负荷的变化。在这里，作者表明，机械敏感的Piezo 1通道作为一个机械换能器，直接将心肌细胞的机械拉伸转化为Ca 2+和ROS信号，从而维持正常的心脏功能。
The beating heart possesses the intrinsic ability to adapt cardiac output to changes in mechanical load. The century-old Frank–Starling law and Anrep effect have documented that stretching the heart during diastolic filling increases its contractile force. However, the molecular mechanotransduction mechanism and its impact on cardiac health and disease remain elusive. Here we show that the mechanically activated Piezo1 channel converts mechanical stretch of cardiomyocytes into Ca2+ and reactive oxygen species (ROS) signaling, which critically determines the mechanical activity of the heart. Either cardiac-specific knockout or overexpression of Piezo1 in mice results in defective Ca2+ and ROS signaling and the development of cardiomyopathy, demonstrating a homeostatic role of Piezo1. Piezo1 is pathologically upregulated in both mouse and human diseased hearts via an autonomic response of cardiomyocytes. Thus, Piezo1 serves as a key cardiac mechanotransducer for initiating mechano-chemo transduction and consequently maintaining normal heart function, and might represent a novel therapeutic target for treating human heart diseases. The beating heart adapts cardiac output to changes in mechanical load via incompletely understood mechanotransduction mechanisms. Here the authors show that the mechanosensitive Piezo1 channel serves as a mechanotransducer for directly converting mechanical stretch of cardiomyocytes into Ca2+ and ROS signaling and consequently maintaining normal heart function.
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影响因子：
20.1
作者：
Iribe G;Ward CW;Camelliti P;Bollensdorff C;Mason F;Burton RA;Garny A;Morphew MK;Hoenger A;Lederer WJ;Kohl P
通讯作者：
Kohl P
由机械敏感离子通道 PIEZO1 和组织力学介导的前馈机制促进胶质瘤侵袭。
影响因子：
16.2
作者：
Chen, Xin;Wanggou, Siyi;Huang, Xi
通讯作者：
Huang, Xi
影响因子：
64.8
作者：
Coste, Bertrand;Xiao, Bailong;Santos, Jose S.;Syeda, Ruhma;Grandl, Joerg;Spencer, Kathryn S.;Kim, Sung Eun;Schmidt, Manuela;Mathur, Jayanti;Dubin, Adrienne E.;Montal, Mauricio;Patapoutian, Ardem
通讯作者：
Patapoutian, Ardem
影响因子：
56.9
作者：
CHENG, H;LEDERER, WJ;CANNELL, MB
通讯作者：
CANNELL, MB
影响因子：
5.5
作者：
Kentish, JC;Wrzosek, A
通讯作者：
Wrzosek, A