小柯机器人

感觉神经元和尿路上皮细胞中的PIEZO2协同调控排尿行为
2020-10-15 16:19

美国斯克里普斯研究所Ardem Patapoutian和美国国立卫生研究院Alexander T. Chesler研究组合作取得一项新突破。他们揭示感觉神经元和尿路上皮细胞中的PIEZO2协同调控排尿行为。2020年10月14日,《自然》在线发表了这项成果。

在本研究中,研究人员发现在下尿道组织中表达敏感离子通道PIEZO2,其对于低阈值膀胱舒张感测和尿道排尿反射是必需的。研究发现PIEZO2是膀胱尿路上皮细胞和受神经支配感觉神经元的传感器。功能性PIEZO2缺失的人和小鼠膀胱调控受损,并且功能性PIEZO2缺失的人还表现出膀胱充盈感不足。这项研究确定PIEZO2是泌尿功能的关键传感因子。这些发现为将来确定尿道上皮细胞与控制排尿的感觉神经元之间的相互作用奠定了基础。

研究人员表示,亨利·米勒(Henry Miller)曾说过“减轻膀胱充盈是人类最大的快乐之一”。排尿对健康至关重要,下尿路疾病会产生较高的病理负担。尽管已有研究揭示调控排尿的大脑中枢回路,但仍缺乏对该过程机制的深入探究。除了受中枢神经系统调控外,控制排尿的排尿反射全都由周围的刺激(如膀胱舒张和尿道流量)引起。在尿路系统中感知拉伸和压力的分子转导机制和细胞类型仍然未知。

附:英文原文

Title: PIEZO2 in sensory neurons and urothelial cells coordinates urination

Author: Kara L. Marshall, Dimah Saade, Nima Ghitani, Adam M. Coombs, Marcin Szczot, Jason Keller, Tracy Ogata, Ihab Daou, Lisa T. Stowers, Carsten G. Bnnemann, Alexander T. Chesler, Ardem Patapoutian

Issue&Volume: 2020-10-14

Abstract: 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 urination1,2,3, 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.

DOI: 10.1038/s41586-020-2830-7

Source: https://www.nature.com/articles/s41586-020-2830-7

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

分享到:

0