Piezo机械敏感性离子通道在膀胱过度活动症中的研究进展

doi:10.3969/j.issn.1006-7795.2025.04.025

摘要/Abstract

摘要： 探究膀胱过度活动(overactive bladder, OAB)中Piezo机械敏感性离子通道的角色，给膀胱功能障碍的临床治疗提供新的思路。本文系统地综述了Piezo1和Piezo2在膀胱中的重要性/作用和特点，包括它们的生物物理特性、位置和功能，并特别关注了它们与OAB病理生理的联系。尽管要完全揭示Piezo通道调节膀胱功能的确切机制为时尚早，但根据现有研究，通过抑制Piezo1/2通道来改变排尿功能可能成为OAB的一种新的治疗策略。随着对Piezo通道的深入研究，其无疑将会成为治疗OAB的潜在靶点和治疗策略。

关键词: 机械敏感阳离子通道, Piezo1, Piezo2, 膀胱过度活动症, 尿路上皮, 尿失禁

Abstract: In order to explore the role of Piezo mechanosensitive ion channel in overactive bladder (OAB), it provides a new idea for the clinical treatment of bladder dysfunction. This paper systematically reviews the importance and characteristics of Piezo1 and Piezo2 in the bladder, including their biophysical properties, localization, and function, with a particular focus on their connection to the pathophysiology of OAB. Although it is still too early to fully uncover the exact mechanism by which the Piezo channel regulates bladder function, altering urination function by inhibiting the Piezo1/2 channel as a new therapeutic strategy for OAB, based on existing research. With the further study of Piezo channel, it will undoubtedly become a potential target and therapeutic strategy for the treatment of OAB.

Key words: mechanosensitive cation channels, Piezo1, Piezo2, overactive bladder, urothelium, urinary incontinence

中图分类号:

史佳卉. Piezo机械敏感性离子通道在膀胱过度活动症中的研究进展[J]. 首都医科大学学报, 2025, 46(4): 749-753.

Shi Jiahui. Research progress of Piezo mechanosensitive ion channel in overactive bladder[J]. Journal of Capital Medical University, 2025, 46(4): 749-753.

参考文献

［1］Coste B, Mathur J, Schmidt M, et al. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels［J］. Science, 2010, 330(6000): 55－60.
［2］Martinac B. 2021 Nobel Prize for mechanosensory transduction［J］. Biophys Rev, 2022, 14(1): 15－20.
［3］Coste B, Xiao B L, Santos J S, et al. Piezo proteins are pore-forming subunits of mechanically activated channels［J］. Nature, 2012, 483(7388): 176－181.
［4］Kefauver J M, Ward A B, Patapoutian A. Discoveries in structure and physiology of mechanically activated ion channels［J］. Nature, 2020, 587(7835): 567－576.
［5］Fang X Z, Zhou T, Xu J Q, et al. Structure, kinetic properties and biological function of mechanosensitive piezo channels［J］. Cell Biosci, 2021, 11(1): 13.
［6］Alper S L. Genetic diseases of Piezo1 and Piezo2 dysfunction［J］. Curr Top Membr, 2017, 79: 97－134.
［7］Murthy S E, Dubin A E, Patapoutian A. Piezos thrive under pressure: mechanically activated ion channels in health and disease［J］. Nat Rev Mol Cell Biol, 2017, 18(12): 771－783.
［8］Wang L, Zhou H, Zhang M M, et al. Structure and mechanogating of the mammalian tactile channel Piezo2［J］. Nature, 2019, 573(7773): 225－229.
［9］Yang X Z, Lin C, Chen X D, et al. Structure deformation and curvature sensing of Piezo1 in lipid membranes［J］. Nature, 2022, 604(7905): 377－383.
［10］Saotome K, Murthy S E, Kefauver J M, et al. Structure of the mechanically activated ion channel Piezo1［J］. Nature, 2018, 554(7693): 481－486.
［11］Lin Y C, Guo Y R, Miyagi A, et al. Force-induced conformational changes in Piezo1［J］. Nature, 2019, 573(7773): 230－234.
［12］Servin-Vences M R, Richardson J, Lewin G R, et al. Mechanoelectrical transduction in chondrocytes［J］. Clin Exp Pharmacol Physiol, 2018, 45(5): 481－488.
［13］Botello-Smith W M, Jiang W J, Zhang H, et al. A mechanism for the activation of the mechanosensitive Piezo1 channel by the small molecule Yoda1［J］. Nat Commun, 2019, 10(1): 4503.
［14］Wu J, Lewis A H, Grandl J. Touch, tension, and transduction-the function and regulation of piezo ion channels［J］. Trends Biochem Sci, 2017, 42(1): 57－71.
［15］Dalghi M G, Ruiz W G, Clayton D R, et al. Functional roles for Piezo1 and Piezo2 in urothelial mechanotransduction and lower urinary tract interoception［J］. JCI Insight, 2021, 6(19): e152984.
［16］Gailly P, Devuyst O. PIEZO2, a mechanosensor in the urinary bladder［J］. Kidney Int, 2021, 100(1): 9－11.
［17］Handler A, Ginty D D. The mechanosensory neurons of touch and their mechanisms of activation［J］. Nat Rev Neurosci, 2021, 22(9): 521－537.
［18］Kim S E, Coste B, Chadha A, et al. The role of Drosophila piezo in mechanical nociception［J］. Nature, 2012, 483(7388): 209－212.
［19］Woo S H, Ranade S, Weyer A D, et al. Piezo2 is required for Merkel-cell mechanotransduction［J］. Nature, 2014, 509(7502): 622－626.
［20］Gnanasambandam R, Ghatak C, Yasmann A, et al. GsMTx4: mechanism of inhibiting mechanosensitive ion channels［J］. Biophys J, 2017, 112(1): 31－45.
［21］Dalghi M G, Clayton D R, Ruiz W G, et al. Expression and distribution of Piezo1 in the mouse urinary tract［J］. Am J Physiol Renal Physiol, 2019, 317(2): F303-F321.
［22］Marshall K L, Saade D, Ghitani N, et al. Piezo2 in sensory neurons and urothelial cells coordinates urination［J］. Nature, 2020, 588(7837): 290－295.
［23］Li X, Hu J W, Yin P, et al. Mechanotransduction in the urothelium: ATP signalling and mechanoreceptors［J］. Heliyon, 2023, 9(9): e19427.
［24］Miyamoto T, Mochizuki T, Nakagomi H, et al. Functional role for Piezo1 in stretch-evoked Ca2+ influx and ATP release in urothelial cell cultures［J］. J Biol Chem, 2014, 289(23): 16565－16575.
［25］Aresta Branco M S L, Gutierrez Cruz A, Peri L E, et al. The pannexin 1 channel and the P2X7 receptor are in complex interplay to regulate the release of soluble ectonucleotidases in the murine bladder lamina propria［J］. Int J Mol Sci, 2023, 24(12): 9964.
［26］Ishizuka Y, Satake Y, Kimura S, et al. Statin administration ameliorates ischemia-induced overactive bladder with improvement of blood flow and anti-inflammatory effects in rats［J］. Neurourol Urodyn, 2024, 43(4): 991－1002.
［27］Clearwater W, Kassam F, Aalami Harandi A, et al. Combination and novel pharmacologic agents for OAB［J］. Curr Urol Rep, 2022, 23(7): 129－141.
［28］Ihara T, Mitsui T, Nakamura Y, et al. The oscillation of intracellular Ca2+ influx associated with the circadian expression of Piezo1 and TRPV4 in the bladder urothelium［J］. Sci Rep, 2018, 8(1): 5699.
［29］Ihara T, Mitsui T, Nakamura Y, et al. Clock genes regulate the circadian expression of piezo1, TRPV4, connexin26, and VNUT in an ex vivo mouse bladder mucosa［J］. PLoS One, 2017, 12(1): e0168234.
［30］Ihara T, Mitsui T, Shimura H, et al. Different effects of GsMTx4 on nocturia associated with the circadian clock and Piezo1 expression in mice［J］. Life Sci, 2021, 278: 119555.
［31］Michishita M, Yano K, Tomita K I, et al. Piezo1 expression increases in rat bladder after partial bladder outlet obstruction［J］. Life Sci, 2016, 166: 1－7.
［32］Mochizuki T, Sokabe T, Araki I, et al. The TRPV4 cation channel mediates stretch-evoked Ca2+ influx and ATP release in primary urothelial cell cultures［J］. J Biol Chem, 2009, 284(32): 21257－21264.
［33］Wang Y F, Chi S P, Guo H F, et al. A lever-like transduction pathway for long-distance chemical- and mechano-gating of the mechanosensitive Piezo1 channel［J］. Nat Commun, 2018, 9(1): 1300.
［34］Merrill L, Gonzalez E J, Girard B M, et al. Receptors, channels, and signalling in the urothelial sensory system in the bladder［J］. Nat Rev Urol, 2016, 13(4): 193－204.
［35］Peyronnet B, Mironska E, Chapple C, et al. A comprehensive review of overactive bladder pathophysiology: on the way to tailored treatment［J］. Eur Urol, 2019, 75(6): 988－1000.
［36］Chesler A T, Szczot M, Bharucha-Goebel D, et al. The role of Piezo2 in human mechanosensation［J］. N Engl J Med, 2016, 375(14): 1355－1364.