The Expression and Function of Piezo Channels in Bladder

Main Article Content

Zhipeng Li
Dongxu Lin
Changcheng Luo
Pengyu Wei
Bolang Deng
Kang Li
Langqing Cheng
Zhong Chen

Keywords

Bladder dysfunction, Mechanosensitive cation channels, Piezo channels

Abstract

The ability for bladder to perceive and analyze mechanical stimuli, such as stretch and filling, is crucial for its functions, such as urinary storage and voiding. The Piezo channel family, including Piezo1 and Piezo2, represents one of the most essential mechanosensitive ion channels in mammals and is involved in a wide array of physiological and pathological processes. It has been demonstrated in numerous investigations that Piezo channels play a key role in mechanical transduction in various types of cells in bladder by converting mechanical stimuli into biological signals. Notably, mounting evidence suggests that Piezo channels are functionally significant for bladder and are related to several bladder disorders. This review systematically summarizes the importance/role and features of Piezo channels in bladder, including their biophysical properties, location, and functions, with attention specifically paid to their association with the physiology and pathophysiology of bladder. This review aims to provide a novel perspective for the future clinical treatment of bladder dysfunction.

Metrics

Metrics Loading ...
Abstract 65 | HTML Downloads 3 PDF Downloads 48

References

1. Vanneste M, Segal A, Voets T, Everaerts W. Transient receptor potential channels in sensory mechanisms of the lower urinary tract. Nat Rev Urol. 2021 Mar;18(3): -139–159. doi:10.1038/s41585-021-00428-6 https://doi.org/10.1038/s41585-021-00428-6 PMID:33536636
2. Griffiths D. Neural control of micturition in humans: a working model. Nat Rev Urol. 2015(Dec);12:695–705.doi:10.1038/nrurol.2015.266 https://doi.org/10.1038/nrurol.2015.266 PMID:26620610
3. Bagriantsev SN, Gracheva EO, Gallagher PG. Piezo proteins: regulators of mechanosensation and other cellular processes. J Biol Chem. 2014 Nov;289(46):31673–81. https://doi.org/10.1074/jbc.R114.612697 PMID:25305018
4. Li X, Hu J, Zhao X, Li J, Chen Y. Piezo channels in the urinary system. Exp Mol Med. 2022 Jun;54(6): 697–710. doi:10.1038/s12276-022-00777-1 https://doi.org/10.1038/s12276-022-00777-1 PMID:35701561
5. Coste B, Mathur J, Schmidt M, Earley TJ, Ranade S, Petrus MJ, et al. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. 2010Oct;330(6000): 55–60. https://doi.org/10.1126/science.1193270 PMID:20813920
6. Savadipour A, Palmer D, Ely EV, Collins KH, Garcia-Castorena JM, Harissa Z, et al. The role of PIEZO ion channels in the musculoskeletal system. Am J Physiol Cell Physiol. 2023 Mar;324(3):C: 728–40. https://doi.org/10.1152/ajpcell.00544.2022 PMID:36717101
7. Zeng W-Z, Marshall KL, Min S, Daou I, Chapleau MW, Abboud FM, et al. PIEZOs mediate neuronal sensing of blood pressure and the baroreceptor reflex. Science. 2018 Oct;362(6413):464–467.10.1126/science.aau6324 https://doi.org/10.1126/science.aau6324 PMID:30361375
8. Reeh PW, Fischer MJM. Nobel somatosensations and pain. Pfluger Arch. 2022Apr;474(4): 405–20. https://doi.org/10.1007/s00424-022-02667-x PMID:35157132
9. Lin YC, Guo YR, Miyagi A, Levring J, MacKinnon R, Scheuring S. Force-induced conformational changes in PIEZO1. Nature. 2019;573: 230–34. https://doi.org/10.1038/s41586-019-1499-2 PMID:31435018
10. Servin-Vences MR, Richardson J, Lewin GR, Poole K. Mechanoelectrical transduction in chondrocytes. Clin Exp Pharmacol Physiol. 2018May;45(5): 481–88. https://doi.org/10.1111/1440-1681.12917 PMID:29359488
11. Murthy SE, Dubin AE, Patapoutian A. Piezos thrive under pressure: mechanically activated ion channels in health and disease. Nat Rev Mol Cell Biol. 2017Dec;18(12): 771–83.https://doi.org/10.1038/nrm.2017.92 PMID:28974772
12. Syeda R, Florendo MN, Cox CD, Kefauver JM, Santos JS, Martinac B, et al. Piezo1 Channels Are Inherently Mechanosensitive. Cell Rep. 2016Nov;17(7): 1739–46. https://doi.org/10.1016/j.celrep.2016.10.033 PMID:27829145
13. Lewis AH, Grandl J. Mechanical sensitivity of Piezo1 ion channels can be tuned by cellular membrane tension. eLife. 2015Dec;4: e12088. https://doi.org/10.7554/eLife.12088 PMID:26646186
14. Gaub BM, Müller DJ. Mechanical Stimulation of Piezo1 Receptors Depends on Extracellular Matrix Proteins and Directionality of Force. Nano Lett. 2017Mar;17(3): 2064–2072. https://doi.org/10.1021/acs.nanolett.7b00177 PMID:28164706
15. Wu J, Lewis AH, Grandl J. Touch, Tension, and Transduction – The Function and Regulation of Piezo Ion Channels. Trends Biochem Sci. 2017Jan;42(1): 57–71. https://doi.org/10.1016/j.tibs.2016.09.004 PMID:27743844
16. Liu Q, Sun B, Zhao J, Wang Q, An F, Hu X, et al. Increased Piezo1 channel activity in interstitial Cajal-like cells induces bladder hyperactivity by functionally interacting with NCX1 in rats with cyclophosphamide-induced cystitis. Exp Mol Med. 2018May;50(5): 1–16. https://doi.org/10.1038/s12276-018-0088-z PMID:29735991
17. Dalghi MG, Ruiz WG, Clayton DR, Montalbetti N, Daugherty SL, Beckel JM, et al. Functional roles for PIEZO1 and PIEZO2 in urothelial mechanotransduction and lower urinary tract interoception. JCI Insight. 2021Oct;6(19): e152984. https://doi.org/10.1172/jci.insight.152984 PMID:34464353
18. Gailly P, Devuyst O. PIEZO2, a mechanosensor in the urinary bladder. Kidney Int. 2021Jul;100(1): 9–11. https://doi.org/10.1016/j.kint.2021.02.021 PMID:33667505
19. Wang Y, Chi S, Guo H, Li G, Wang L, Zhao Q, et al. A lever-like transduction pathway for long-distance chemical- and mechano-gating of the mechanosensitive Piezo1 channel. Nat Commun. 2018Apr;9(1): 1300. https://doi.org/10.1038/s41467-018-03570-9 PMID:29610524
20. Woo SH, Ranade S, Weyer AD, Dubin AE, Baba Y, Qiu Z, et al. Piezo2 is required for Merkel-cell mechanotransduction. Nature. 2014May;509(7502): 622–26. https://doi.org/10.1038/nature13251 PMID:24717433
21. Kim SE, Coste B, Chadha A, Cook B, Patapoutian A. The role of Drosophila Piezo in mechanical nociception. Nature. 2012Feb;483(7388): 209–12. https://doi.org/10.1038/nature10801 PMID:22343891
22. Ranade SS, Woo SH, Dubin AE, Moshourab RA, Wetzel C, Petrus M, et al. Piezo2 is the major transducer of mechanical forces for touch sensation in mice. Nature. 2014Dec;516(7529): 121–25. https://doi.org/10.1038/nature13980 PMID:25471886
23. Woo SH, Lukacs V, de Nooij JC, Zaytseva D, Criddle CR, Francisco A, et al. Piezo2 is the principal mechanotransduction channel for proprioception. Nat Neurosci. 2015Dec;18(12): 1756–1762. https://doi.org/10.1038/nn.4162 PMID:26551544
24. Dalghi MG, Clayton DR, Ruiz WG, Al-bataineh MM, Satlin LM, Kleyman TR, et al. Expression and distribution of PIEZO1 in the mouse urinary tract. Am J Physiol-Renal Physiol.2019Aug;317(2):F303–21. https://doi.org/10.1152/ajprenal.00214.2019 PMID:31166705
25. Dalghi MG, Montalbetti N, Carattino MD, Apodaca G. The Urothelium: Life in a Liquid Environment. Physiol Rev. 2020Oct;100(4): 1621–705. https://doi.org/10.1152/physrev.00041.2019 PMID:32191559
26. Marshall KL, Saade D, Ghitani N, Coombs AM, Szczot M, Keller J, et al. PIEZO2 in sensory neurons and urothelial cells coordinates urination. Nature. 2020Dec;588(7837): 290–95. https://doi.org/10.1038/s41586-020-2830-7 PMID:33057202
27. Dunning-Davies BM, Fry CH, Mansour D, Ferguson DR. The regulation of ATP release from the urothelium by adenosine and transepithelial potential: Adenosine and ATP release from the urothelium. BJU Int. 2013Mar;111(3): 505–13. https://doi.org/10.1111/j.1464-410X.2012.11421.x PMID:22882496
28. Mochizuki T, Sokabe T, Araki I, Fujishita K, Shibasaki K, Uchida K, et al. The TRPV4 cation channel mediates stretch-evoked Ca2+ influx and ATP release in primary urothelial cell cultures. J Biol Chem. 2009 Aug;284(32):21257–64. https://doi.org/10.1074/jbc.M109.020206 PMID:19531473
29. Aresta Branco MS, Gutierrez Cruz A, Peri LE, Mutafova-Yambolieva VN. 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. Int J Mol Sci. 2023 Jun;24(12):9964. https://doi.org/10.3390/ijms24129964 PMID:37373111
30. Wei L, Mousawi F, Li D, Roger S, Li J, Yang X, et al. Adenosine Triphosphate Release and P2 Receptor Signaling in Piezo1 Channel-Dependent Mechanoregulation. Front Pharmacol. 2019Nov;10: 1304. https://doi.org/10.3389/fphar.2019.01304 PMID:31780935
31. Vlaskovska M, Kasakov L, Rong W, Bodin P, Bardini M, Cockayne DA, et al. P2X3 knock-out mice reveal a major sensory role for urothelially released ATP. J Neurosci. 2001 Aug;21(15):5670–7. https://doi.org/10.1523/JNEUROSCI.21-15-05670.2001 PMID:11466438
32. Birder L, Andersson KE. Urothelial Signaling. Physiol Rev. 2013Apr;93(2):653-80. https://doi.org/10.1152/physrev.00030.2012 PMID:23589830
33. Kefauver JM, Ward AB, Patapoutian A. Discoveries in structure and physiology of mechanically activated ion channels. Nature. 2020Nov;587(7835): 567–76. https://doi.org/10.1038/s41586-020-2933-1 PMID:33239794
34. Zhao M, Chen Z, Liu L, Ding N, Wen J, Liu J, et al. Functional Expression of Transient Receptor Potential and Piezo1 Channels in Cultured Interstitial Cells of Human-Bladder Lamina Propria. Front Physiol. 2022Jan;12: 762847. https://doi.org/10.3389/fphys.2021.762847 PMID:35069237
35. McCubbin S, Jeoung A, Waterbury C, Cooper RL. Pharmacological profiling of stretch activated channels in proprioceptive neurons. Comp Biochem Physiol Part C Toxicol Pharmacol. 2020Jul;233:108765. https://doi.org/10.1016/j.cbpc.2020.108765 PMID:32305458
36. Miyamoto T, Mochizuki T, Nakagomi H, Kira S, Watanabe M, Takayama Y, et al. Functional Role for Piezo1 in stretch-evoked Ca2+ Influx and ATP release in urothelial cell cultures. J Biol Chem. 2014Jun;289(23): 16565–16575. https://doi.org/10.1074/jbc.M113.528638 PMID:24759099
37. Wang S, Chennupati R, Kaur H, Iring A, Wettschureck N, Offermanns S. Endothelial cation channel PIEZO1 controls blood pressure by mediating flow-induced ATP release. J Clin Invest. 2016Dec;126(12): 4527–4536. https://doi.org/10.1172/JCI87343 PMID:27797339
38. Skryma R, Prevarskaya N, Gkika D, Shuba Y. From urgency to frequency: facts and controversies of TRPs in the lower urinary tract. Nat Rev Urol. 2011Oct;8(11): 617–30. https://doi.org/10.1038/nrurol.2011.142 PMID:21971315
39. Thorneloe KS, Sulpizio AC, Lin Z, Figueroa DJ, Clouse AK, McCafferty GP, et al. N-((1S)-1-{[4-((2S)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a novel and potent transient receptor potential vanilloid 4 channel agonist induces urinary bladder contraction and hyperactivity: Part I. J Pharmacol Exp Ther. 2008Aug;326(2): 432–442. https://doi.org/10.1124/jpet.108.139295 PMID:18499743
40. Michishita M, Yano KI, Tomita K, Matsuzaki O, Kasahara K. Piezo1 expression increases in rat bladder after partial bladder outlet obstruction. Life Sci. 2016Dec;166: 1–7. https://doi.org/10.1016/j.lfs.2016.10.017 PMID:27756599
41. Merrill L, Gonzalez EJ, Girard BM, Vizzard MA. Receptors, channels, and signalling in the urothelial sensory system in the bladder. Nat Rev Urol. 2016Apr;13(4): 193–204. https://doi.org/10.1038/nrurol.2016.13 PMID:26926246
42. Chesler AT, Szczot M, Bharucha-Goebel D, Čeko M, Donkervoort S, Laubacher C, et al. The Role of PIEZO2 in Human Mechanosensation. N Engl J Med. 2016Oct;375(14): 1355–1364. https://doi.org/10.1056/NEJMoa1602812 PMID:27653382
43. Wang W, Ai J, Liao B, Xiao K, Lin L, Chen H, et al. The roles of MCP-1/CCR2 mediated macrophage recruitment and polarization in bladder outlet obstruction (BOO) induced bladder remodeling. Int Immunopharmacol. 2021Oct;99: 107947. https://doi.org/10.1016/j.intimp.2021.107947 PMID:34311189
44. Metcalfe PD, Wang J, Jiao H, Huang Y, Hori K, Moore RB, et al. Bladder outlet obstruction: progression from inflammation to fibrosis. BJU Int. 2010Dec;106(11): 1686–1694. https://doi.org/10.1111/j.1464-410X.2010.09445.x PMID:20590549
45. Gratzke C, Bachmann A, Descazeaud A, Drake MJ, Madersbacher S, Mamoulakis C, et al. EAU Guidelines on the Assessment of Non-neurogenic Male Lower Urinary Tract Symptoms including Benign Prostatic Obstruction. Eur Urol. 2015Jun;67(6): 1099–1109. https://doi.org/10.1016/j.eururo.2014.12.038 PMID:25613154
46. Baker SA, Hatton WJ, Han J, Hennig GW, Britton FC, Koh SD. Role of TREK-1 potassium channel in bladder overactivity after partial bladder outlet obstruction in Mmouse. J Urol. 2010Fen;183(2): 793–800. https://doi.org/10.1016/j.juro.2009.09.079 PMID:20022044
47. Cho KJ, Park EY, Kim HS, Koh JS, Kim JC. Expression of transient receptor potential vanilloid 4 and effects of ruthenium red on detrusor overactivity associated with bladder outlet obstruction in rats. World J Urol. 2014jun;32(3): 677–682. https://doi.org/10.1007/s00345-013-1099-y PMID:23700140
48. Wiseman OJ, Fowler CJ, Landon DN. The role of the human bladder lamina propria myofibroblast. BJU Int. 2003Jan;91(1): 89–93. https://doi.org/10.1046/j.1464-410X.2003.03802.x PMID:12614258
49. Birder LA, de Groat WC. Mechanisms of Disease: involvement of the urothelium in bladder dysfunction. Nat Clin Pract Urol. 2007Jan;4(1): 46–54. https://doi.org/10.1038/ncpuro0672 PMID:17211425
50. Hawthorn MH, Chapple CR, Cock M, Chess-Williams R. Urothelium-derived inhibitory factor(s) in¯uences on detrusor muscle contractility in vitro. Br J Pharmacol. 129.
51. Lee SR, Kim HJ, Kim A, Kim JH. Overactive bladder is not only overactive but also hypersensitive. Urology. 2010 May;75(5):1053–9. https://doi.org/10.1016/j.urology.2009.10.045 PMID:20092879 PMID:30922690
52. Peyronnet B, Mironska E, Chapple C, Cardozo L, Oelke M, Dmochowski R, et al. A Comprehensive Review of Overactive Bladder Pathophysiology: On the Way to Tailored Treatment. Eur Urol. 2019Jun;75(6): 988–1000. https://doi.org/10.1016/j.eururo.2019.02.038 PMID:30922690
53. Gevaert T, Vriens J, Segal A, Everaerts W, Roskams T, Talavera K, et al. Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding. J Clin Invest. 2007Nov;117(11): 3453–62. https://doi.org/10.1172/JCI31766 PMID:17948126
54. Ramsay S, Zagorodnyuk V. Role of circadian rhythms and melatonin in bladder function in heath and diseases. Auton Neurosci. 2023 May;246:103083. https://doi.org/10.1016/j.autneu.2023.103083 PMID:36871511
55. Herrera GM, Meredith AL. Diurnal Variation in Urodynamics of Rat. Yamazaki S, editor. PLoS ONE. 2010;5: e12298. https://doi.org/10.1371/journal.pone.0012298.
56. Parsons M, Tissot W, Cardozo L, Diokno A, Amundsen CL, Coats AC, et al. Bladder Diary Research Team Normative bladder diary measurements: Night versus day: Normative Day and Night Bladder Diary Measurements. Neurourol Urodyn. 2007;26(4): 465–473.https://doi.org/10.1002/nau.20355 PMID:17335055
57. Ihara T, Mitsui T, Nakamura Y, Kanda M, Tsuchiya S, Kira S, et al. The oscillation of intracellular Ca2+ influx associated with the circadian expression of Piezo1 and TRPV4 in the bladder urothelium. Sci Rep. 2018Apr;8(1): 5699. https://doi.org/10.1038/s41598-018-23115-w PMID:29632308
58. Ihara T, Mitsui T, Nakamura Y, Kira S, Nakagomi H, Sawada N, et al. Clock Genes Regulate the Circadian Expression of Piezo1, TRPV4, Connexin26, and VNUT in an Ex Vivo Mouse Bladder Mucosa. Bartell PA, editor. PLOS ONE. 2017;12: e0168234. https://doi.org/10.1371/journal.pone.0168234
59. Ihara T, Mitsui T, Shimura H, Tsuchiya S, Kanda M, Kira S, et al. Different effects of GsMTx4 on nocturia associated with the circadian clock and Piezo1 expression in mice. Life Sci. 202Aug 1;278: 119555. https://doi.org/10.1016/j.lfs.2021.119555 PMID:33930366
60. Gudipaty SA, Lindblom J, Loftus PD, Redd MJ, Edes K, Davey CF, et al. Mechanical stretch triggers rapid epithelial cell division through Piezo1. Nature. 2017Mar;543(7643): 118–21. https://doi.org/10.1038/nature21407 PMID:28199303
61. Kun Z, Fang K, Fei Y, Bo Y, Li-Jun Y, Fu-Li W, et al. Effects of diabetes mellitus on the Piezo ion channels in rat bladder tissues. J Mod Urol. 2018.
62. Compérat E, Amin MB, Cathomas R, Choudhury A, De Santis M, Kamat A, et al. Current best practice for bladder cancer: a narrative review of diagnostics and treatments. The Lancet. 2022Nov;400(10364): 1712–1721. https://doi.org/10.1016/S0140-6736(22)01188-6 PMID:36174585
63. Etem E, Ceylan GG, Özaydın S, Ceylan C, Özercan I, Kuloğlu T. The increased expression of Piezo1 and Piezo2 ion channels in human and mouse bladder carcinoma. Adv Clin Exp Med. 2018Aug;27(8): 1025–31. https://doi.org/10.17219/acem/71080 PMID:30010255
64. De Felice D, Alaimo A. Mechanosensitive Piezo Channels in Cancer: Focus on altered Calcium Signaling in Cancer Cells and in Tumor Progression. Cancers. 2020Jul;12(7): 1780. https://doi.org/10.3390/cancers12071780 PMID:32635333
65. Guo J, Gu D, Zhao T, Zhao Z, Xiong Y, Sun M, et al. Trends in Piezo Channel Research Over the Past Decade: A Bibliometric Analysis. Front Pharmacol. 2021Apr;12: 668714. https://doi.org/10.3389/fphar.2021.668714 PMID:33935792