Henry Miller stated that "to relieve a full bladder is one of the great human joys". Urination is critically important in health and ailments of the lower urinary tract cause high pathological burden. Although there have been advances in understanding the central circuitry in the brain that facilitates urination1-3, there is a lack of in-depth mechanistic insight into the process. In addition to central control, micturition reflexes that govern urination are all initiated by peripheral mechanical stimuli such as bladder stretch and urethral flow4. The mechanotransduction molecules and cell types that function as the primary stretch and pressure detectors in the urinary tract mostly remain unknown. Here we identify expression of the mechanosensitive ion channel PIEZO2 in lower urinary tract tissues, where it is required for low-threshold bladder-stretch sensing and urethral micturition reflexes. We show that PIEZO2 acts as a sensor in both the bladder urothelium and innervating sensory neurons. Humans and mice lacking functional PIEZO2 have impaired bladder control, and humans lacking functional PIEZO2 report deficient bladder-filling sensation. This study identifies PIEZO2 as a key mechanosensor in urinary function. These findings set the foundation for future work to identify the interactions between urothelial cells and sensory neurons that control urination.

中文翻译：

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感觉神经元和尿路上皮细胞中的 PIEZO2 协调排尿

亨利·米勒表示“缓解膀胱充盈是人类最大的乐趣之一”。排尿对于健康至关重要，下尿路疾病会导致较高的病理负担。尽管在理解大脑中促进排尿的中央回路方面取得了进展1-3，但对该过程缺乏深入的机制了解。除了中枢控制外，控制排尿的排尿反射都是由外周机械刺激（例如膀胱拉伸和尿道流量）启动的。在泌尿道中充当主要拉伸和压力检测器的机械转导分子和细胞类型大多仍然未知。在这里，我们确定了下尿路组织中机械敏感离子通道 PIEZO2 的表达，需要低阈值膀胱牵张感测和尿道排尿反射。我们证明 PIEZO2 在膀胱尿路上皮和支配感觉神经元中充当传感器。缺乏功能性 PIEZO2 的人类和小鼠的膀胱控制受损，而缺乏功能性 PIEZO2 的人类报告膀胱充盈感不足。这项研究将 PIEZO2 确定为泌尿功能的关键机械传感器。这些发现为未来确定尿路上皮细胞和控制排尿的感觉神经元之间的相互作用奠定了基础。缺乏功能性 PIEZO2 的人类报告膀胱充盈感不足。这项研究将 PIEZO2 确定为泌尿功能的关键机械传感器。这些发现为未来确定尿路上皮细胞和控制排尿的感觉神经元之间的相互作用奠定了基础。缺乏功能性 PIEZO2 的人类报告膀胱充盈感不足。这项研究将 PIEZO2 确定为泌尿功能的关键机械传感器。这些发现为未来确定尿路上皮细胞和控制排尿的感觉神经元之间的相互作用奠定了基础。