The mechanosensitive ion channel PIEZO1 is expressed in tendons and regulates physical performance
The mechanosensitive ion channel PIEZO1 is expressed in tendons and regulates physical performance
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机械敏感离子通道PIEZO 1在肌腱中表达并调节身体性能
DOI：
10.1126/scitranslmed.abj5557
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发表时间：
2022-06-01
影响因子：
17.1
通讯作者：
Asahara, Hiroshi
中科院分区：
文献类型：
--
作者：
Nakamichi, Ryo;Ma, Shang;Asahara, Hiroshi
机械应力是如何通过肌腱影响身体表现的，目前还不完全清楚。PIEZO1是一种机械敏感的离子通道，最近发现E756del PIEZO1是一种在非洲人后裔中常见的功能获得变体。我们使用R2482H Piezo1，一种小鼠功能获得变种，产生了肌腱特异的敲入小鼠，并发现它们比野生型或肌肉特异的敲入小鼠有更高的跳跃能力和更快的跑步速度。这些表型与肌腱合成代谢增强有关，这是通过肌腱特异性转录因子莫霍克和硬化轴的增加，但没有证据表明肌肉发生了变化。生物力学分析表明，R2482H Piezo1小鼠的肌腱柔韧性更强，储存了更多的弹性能量，与跳跃能力的增强相一致。这些表型在肌腱成熟后被肌腱特异性R2482H Piezo1替换的小鼠身上复制，表明PIEZO1可能成为通过增强成熟肌腱的功能来促进体能的靶点。在牙买加的一个小队列中，短跑运动员中E756 del PIEZO1的频率高于与人群匹配的非运动对照组，这表明人类也有类似的功能。人类和小鼠的遗传和生理学证据一起揭示了肌腱在身体表现中的关键功能，这一功能受到腱细胞中PIEZO1的严格和强有力的调节。
How mechanical stress affects physical performance via tendons is not fully understood. Piezo1 is a mechanosensitive ion channel, and E756del PIEZO1 was recently found as a gain-of-function variant that is common in individuals of African descent. We generated tendon-specific knock-in mice using R2482H Piezo1, a mouse gain-of-function variant, and found that they had higher jumping abilities and faster running speeds than wild-type or muscle-specific knock-in mice. These phenotypes were associated with enhanced tendon anabolism via an increase in tendon-specific transcription factors, Mohawk and Scleraxis, but there was no evidence of changes in muscle. Biomechanical analysis showed that the tendons of R2482H Piezo1 mice were more compliant and stored more elastic energy, consistent with the enhancement of jumping ability. These phenotypes were replicated in mice with tendon-specific R2482H Piezo1 replacement after tendon maturation, indicating that PIEZO1 could be a target for promoting physical performance by enhancing function in mature tendon. The frequency of E756del PIEZO1 was higher in sprinters than in population-matched nonathletic controls in a small Jamaican cohort, suggesting a similar function in humans. Together, this human and mouse genetic and physiological evidence revealed a critical function of tendons in physical performance, which is tightly and robustly regulated by PIEZO1 in tenocytes.