Functional roles for PIEZO1 and PIEZO2 in urothelial mechanotransduction and lower urinary tract interoception

JCI Insight, Journal Year: 2021, Volume and Issue: 6(19)

Published: Aug. 31, 2021

The mechanisms that link visceral mechanosensation to the perception of internal organ status (i.e., interoception) remain elusive. In response bladder filling, urothelium releases ATP, which is hypothesized stimulate voiding function by communicating degree fullness subjacent tissues, including afferent nerve fibers. To determine if PIEZO channels as mechanosensors in these events, we generated conditional urothelial Piezo1-, Piezo2-, and dual Piezo1/2-knockout (KO) mice. While functional PIEZO1 were expressed all cell layers, Piezo1-KO mice had a limited phenotype. Piezo2 expression was small subset superficial umbrella cells, yet male Piezo2-KO exhibited incontinence leakage) when their behavior monitored during active dark phase. Dual Piezo1/2-KO most affected phenotype, characterized decreased responses mechanical stimulation, diminished ATP release, hypoactivity anesthetized females but not males, urinary both female phase inactive light one. Our studies reveal functions sex- circadian rhythm-dependent manner PIEZO1/2 channel-driven mechanotransduction normal behavior, absence signals, dysfunction ensues.

Language: Английский

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The urothelium: a multi-faceted barrier against a harsh environment

Mucosal Immunology, Journal Year: 2022, Volume and Issue: 15(6), P. 1127 - 1142

Published: Sept. 30, 2022

All mucosal surfaces must deal with the challenge of exposure to outside world. The urothelium is a highly specialized layer stratified epithelial cells lining inner surface urinary bladder, gruelling environment involving significant stretch forces, osmotic and hydrostatic pressures, toxic substances, microbial invasion. bladder plays an important barrier role allows accommodation expulsion large volumes urine without permitting components diffuse across. made up three cell types, basal, intermediate, umbrella cells, whose functions aid in bladder's mission. In this review, we summarize recent insights into urothelial structure, function, development, regeneration, particular formation maintenance. We briefly review diseases which involve discuss current human vitro models as complement traditional animal studies.

Language: Английский

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Advances in Diagnosis and Therapy for Bladder Cancer

Cancers, Journal Year: 2022, Volume and Issue: 14(13), P. 3181 - 3181

Published: June 29, 2022

Bladder cancer (BCa) is one of the most common and expensive urinary system malignancies for its high recurrence progression rate. In recent years, immense amounts studies have been carried out to bring a more comprehensive cognition numerous promising clinic approaches BCa therapy. The development innovative enhanced cystoscopy techniques (optical techniques, imaging systems) tumor biomarkers-based non-invasive urine screening (DNA methylation-based test) would dramatically improve accuracy detection, reducing risk BCa. Moreover, intravesical instillation systemic therapeutic strategies (cocktail therapy, immunotherapy, vaccine targeted therapy) also provide plentiful measures break predicament Several exploratory clinical studies, including novel surgical approaches, pharmaceutical compositions, bladder preservation emerged continually, which are supposed be candidates treatment. Here, advances prospects diagnosis, or treatment, drug delivery systems therapy reviewed in this paper.

Language: Английский

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Current and Emerging Pharmacological Targets and Treatments of Urinary Incontinence and Related Disorders

Pharmacological Reviews, Journal Year: 2023, Volume and Issue: 75(4), P. 554 - 674

Published: March 14, 2023

Overactive bladder syndrome with and without urinary incontinence related conditions, signs, disorders such as detrusor overactivity, neurogenic lower tract dysfunction, underactive bladder, stress incontinence, nocturia are common in the general population have a major impact on quality of life affected patients their partners. Based deliberations subcommittee pharmacological treatments 7th International Consultation Incontinence, we present comprehensive review established drug targets treatment overactive aforementioned conditions approved drugs used its treatment. Investigational compounds also reviewed. We conclude that, despite range available medical options, considerable need continues to exist. This is largely because existing symptomatic limited efficacy and/or tolerability, which leads poor long-term adherence.

Significance Statement

Urinary prevalent population. While many been approved, few stay none them being curative. paper provides discussion emerging options for various types disorders.

Language: Английский

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Tracing the Evolution of Sex Hormones and Receptor‐Mediated Immune Microenvironmental Differences in Prostate and Bladder Cancers: From Embryonic Development to Disease

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Abstract The bladder and prostate originate from the urogenital sinus. However, cancer (BC) is usually classified as an immune “hot” tumor, whereas (PCa) deemed “cold” tumor according to microenvironment (TME) clinical outcomes. To investigate differences between BC PCa, studies are compared focusing on regulation mediated by sex hormones receptors identify key genes pathways responsible for differences. From a developmental perspective, it shown that PCa activate similar those in stage. During development, differential expression function of androgen receptor (AR) across cell types may contribute its dual role promoting inhibiting immunity different cells. Androgen deprivation therapy affects AR cells within TME, influencing infiltration antitumor function. Additionally, estrogenα estrogenβ exert contrasting effects BC, which hold potential modifying phenotypes. Future research should target involved development clarify regulatory similarities PCa.

Language: Английский

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An immunoresponsive three-dimensional urine-tolerant human urothelial model to study urinary tract infection

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: March 27, 2023

Introduction Murine models of urinary tract infection (UTI) have improved our understanding host-pathogen interactions. However, given differences between rodent and human bladders which may modulate host bacterial response, including certain biomarkers, urothelial thickness the concentration urine, development new human-based is important to complement mouse studies provide a more complete picture UTI in patients. Methods We originally developed three-dimensional (3D) model was urine tolerant demonstrated several but it only achieved heterogenous, multi-layered zones did not demonstrate comprehensive differentiation status needed achieve barrier function. optimised this by altering variety conditions validated with microscopy, flow cytometry, transepithelial electrical resistance FITC-dextran permeability assays confirm tissue architecture, integrity response infection. Results an 3D urine-tolerant (3D-UHU), after 18-20 days growth, stratified uniformly 7-8 layers comprised three expected, distinct cell types. The apical surface differentiated into large, CD227+ umbrella-like cells expressing uroplakin-1A, II, III, cytokeratin 20, all are terminal markers, glycosaminoglycan layer. Below layer, intermediate were present, single underlying layer CD271+ basal cells. also expressed E-cadherin, ZO-1, claudin-1 -3, possessed good Infection both Gram-negative Gram-positive classes elicited elevated levels pro-inflammatory cytokines chemokines characteristic humans caused decrease Discussion Taken together, 3D-UHU holds promise for studying interactions immune response.

Language: Английский

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Understanding the cellular dynamics, engineering perspectives and translation prospects in bioprinting epithelial tissues

Bioactive Materials, Journal Year: 2024, Volume and Issue: 43, P. 195 - 224

Published: Sept. 24, 2024

Language: Английский

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From stretch to deflection: the importance of context in the activation of mammalian, mechanically activated ion channels

FEBS Journal, Journal Year: 2021, Volume and Issue: 289(15), P. 4447 - 4469

Published: June 1, 2021

The ability of cells to convert mechanical perturbations into biochemical information is an essential aspect mammalian physiology. molecules that mediate such mechanotransduction include mechanically activated ion channels, which directly inputs electrochemical signals. unifying feature these channels their open probability increases with the application a input. However, structure, activation profile and sensitivity distinct vary from channel channel. In this review, we discuss how ionic currents can be evoked monitored in vitro, describe profiles displayed by range channels. addition, various mechanisms best‐characterized mammalian, channel, PIEZO1, modulated. diversity modulation suggest may facilitate finely controlled diverse sense cells.

Language: Английский

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The Diverse Physiological Functions of Mechanically Activated Ion Channels in Mammals

Annual Review of Physiology, Journal Year: 2021, Volume and Issue: 84(1), P. 307 - 329

Published: Oct. 12, 2021

Many aspects of mammalian physiology are mechanically regulated. One set molecules that can mediate mechanotransduction the activated ion channels. These ionotropic force sensors directly by mechanical inputs, resulting in ionic flux across plasma membrane. While there has been much research focus on role channels touch sensation and hearing, recent data have highlighted broad expression pattern these cells. Disruption shown to impact ( a) development mechanoresponsive structures, b) acute sensing, c) driven homeostatic maintenance multiple tissue types. The diversity processes impacted highlights importance physiology.

Language: Английский

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Potential role of oxidative stress in the pathogenesis of diabetic bladder dysfunction

Nature Reviews Urology, Journal Year: 2022, Volume and Issue: 19(10), P. 581 - 596

Published: Aug. 16, 2022

Language: Английский

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