Dalghi Marianela G, Clayton Dennis R, Ruiz Wily G, Al-Bataineh Mohammad M, Satlin Lisa M, Kleyman Thomas R, Ricke William A, Carattino Marcelo D, Apodaca Gerard
Department of Medicine and George M. O'Brien Pittsburgh Center for Kidney Research, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
Department of Pediatrics, Icahn School of Medicine at Mount Sinai , New York, New York.
Am J Physiol Renal Physiol. 2019 Aug 1;317(2):F303-F321. doi: 10.1152/ajprenal.00214.2019. Epub 2019 Jun 5.
The proper function of the organs that make up the urinary tract (kidneys, ureters, bladder, and urethra) depends on their ability to sense and respond to mechanical forces, including shear stress and wall tension. However, we have limited understanding of the mechanosensors that function in these organs and the tissue sites in which these molecules are expressed. Possible candidates include stretch-activated PIEZO channels (PIEZO1 and PIEZO2), which have been implicated in mechanically regulated body functions including touch sensation, proprioception, lung inflation, and blood pressure regulation. Using reporter mice expressing a COOH-terminal fusion of with the sequence for the tandem-dimer gene, we found that PIEZO1 is expressed in the kidneys, ureters, bladder, and urethra as well as organs in close proximity, including the prostate, seminal vesicles and ducts, ejaculatory ducts, and the vagina. We further found that PIEZO1 expression is not limited to one cell type; it is observed in the endothelial and parietal cells of the renal corpuscle, the basolateral surfaces of many of the epithelial cells that line the urinary tract, the interstitial cells of the bladder and ureters, and populations of smooth and striated muscle cells. We propose that in the urinary tract, PIEZO1 likely functions as a mechanosensor that triggers responses to wall tension.
构成泌尿系统(肾脏、输尿管、膀胱和尿道)的器官的正常功能取决于它们感知和响应机械力的能力,包括剪切应力和壁张力。然而,我们对这些器官中起作用的机械传感器以及这些分子表达的组织部位了解有限。可能的候选者包括拉伸激活的PIEZO通道(PIEZO1和PIEZO2),它们与包括触觉、本体感觉、肺扩张和血压调节在内的机械调节身体功能有关。使用表达与串联二聚体基因序列的COOH末端融合的报告小鼠,我们发现PIEZO1在肾脏、输尿管、膀胱、尿道以及附近器官中表达,包括前列腺、精囊和导管、射精管和阴道。我们进一步发现PIEZO1的表达不限于一种细胞类型;在肾小体的内皮细胞和壁层细胞、许多衬贴尿道的上皮细胞的基底外侧表面、膀胱和输尿管的间质细胞以及平滑肌和横纹肌细胞群体中都观察到了它的表达。我们提出,在泌尿系统中,PIEZO1可能作为一种机械传感器发挥作用,触发对壁张力的反应。