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

The mechanisms that link visceral mechanosensation to the perception of internal organ status (i.e., interoception) remain elusive. In response to bladder filling, the urothelium releases ATP, which is hypothesized to stimulate voiding function by communicating the degree of bladder fullness to subj...

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Autores principales: Dalghi, Marianela G., Ruiz, Wily G., Clayton, Dennis R., Montalbetti, Nicolas, Daugherty, Stephanie L., Beckel, Jonathan M., Carattino, Marcelo D., Apodaca, Gerard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525643/
https://www.ncbi.nlm.nih.gov/pubmed/34464353
http://dx.doi.org/10.1172/jci.insight.152984
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author Dalghi, Marianela G.
Ruiz, Wily G.
Clayton, Dennis R.
Montalbetti, Nicolas
Daugherty, Stephanie L.
Beckel, Jonathan M.
Carattino, Marcelo D.
Apodaca, Gerard
author_facet Dalghi, Marianela G.
Ruiz, Wily G.
Clayton, Dennis R.
Montalbetti, Nicolas
Daugherty, Stephanie L.
Beckel, Jonathan M.
Carattino, Marcelo D.
Apodaca, Gerard
author_sort Dalghi, Marianela G.
collection PubMed
description The mechanisms that link visceral mechanosensation to the perception of internal organ status (i.e., interoception) remain elusive. In response to bladder filling, the urothelium releases ATP, which is hypothesized to stimulate voiding function by communicating the degree of bladder fullness to subjacent tissues, including afferent nerve fibers. To determine if PIEZO channels function as mechanosensors in these events, we generated conditional urothelial Piezo1-, Piezo2-, and dual Piezo1/2-knockout (KO) mice. While functional PIEZO1 channels were expressed in all urothelial cell layers, Piezo1-KO mice had a limited phenotype. Piezo2 expression was limited to a small subset of superficial umbrella cells, yet male Piezo2-KO mice exhibited incontinence (i.e., leakage) when their voiding behavior was monitored during their active dark phase. Dual Piezo1/2-KO mice had the most affected phenotype, characterized by decreased urothelial responses to mechanical stimulation, diminished ATP release, bladder hypoactivity in anesthetized Piezo1/2-KO females but not males, and urinary incontinence in both male and female Piezo1/2-KO mice during their dark phase but not inactive light one. Our studies reveal that the urothelium functions in a sex- and circadian rhythm–dependent manner to link urothelial PIEZO1/2 channel–driven mechanotransduction to normal voiding function and behavior, and in the absence of these signals, bladder dysfunction ensues.
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spelling pubmed-85256432021-10-26 Functional roles for PIEZO1 and PIEZO2 in urothelial mechanotransduction and lower urinary tract interoception Dalghi, Marianela G. Ruiz, Wily G. Clayton, Dennis R. Montalbetti, Nicolas Daugherty, Stephanie L. Beckel, Jonathan M. Carattino, Marcelo D. Apodaca, Gerard JCI Insight Research Article The mechanisms that link visceral mechanosensation to the perception of internal organ status (i.e., interoception) remain elusive. In response to bladder filling, the urothelium releases ATP, which is hypothesized to stimulate voiding function by communicating the degree of bladder fullness to subjacent tissues, including afferent nerve fibers. To determine if PIEZO channels function as mechanosensors in these events, we generated conditional urothelial Piezo1-, Piezo2-, and dual Piezo1/2-knockout (KO) mice. While functional PIEZO1 channels were expressed in all urothelial cell layers, Piezo1-KO mice had a limited phenotype. Piezo2 expression was limited to a small subset of superficial umbrella cells, yet male Piezo2-KO mice exhibited incontinence (i.e., leakage) when their voiding behavior was monitored during their active dark phase. Dual Piezo1/2-KO mice had the most affected phenotype, characterized by decreased urothelial responses to mechanical stimulation, diminished ATP release, bladder hypoactivity in anesthetized Piezo1/2-KO females but not males, and urinary incontinence in both male and female Piezo1/2-KO mice during their dark phase but not inactive light one. Our studies reveal that the urothelium functions in a sex- and circadian rhythm–dependent manner to link urothelial PIEZO1/2 channel–driven mechanotransduction to normal voiding function and behavior, and in the absence of these signals, bladder dysfunction ensues. American Society for Clinical Investigation 2021-10-08 /pmc/articles/PMC8525643/ /pubmed/34464353 http://dx.doi.org/10.1172/jci.insight.152984 Text en © 2021 Dalghi et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Dalghi, Marianela G.
Ruiz, Wily G.
Clayton, Dennis R.
Montalbetti, Nicolas
Daugherty, Stephanie L.
Beckel, Jonathan M.
Carattino, Marcelo D.
Apodaca, Gerard
Functional roles for PIEZO1 and PIEZO2 in urothelial mechanotransduction and lower urinary tract interoception
title Functional roles for PIEZO1 and PIEZO2 in urothelial mechanotransduction and lower urinary tract interoception
title_full Functional roles for PIEZO1 and PIEZO2 in urothelial mechanotransduction and lower urinary tract interoception
title_fullStr Functional roles for PIEZO1 and PIEZO2 in urothelial mechanotransduction and lower urinary tract interoception
title_full_unstemmed Functional roles for PIEZO1 and PIEZO2 in urothelial mechanotransduction and lower urinary tract interoception
title_short Functional roles for PIEZO1 and PIEZO2 in urothelial mechanotransduction and lower urinary tract interoception
title_sort functional roles for piezo1 and piezo2 in urothelial mechanotransduction and lower urinary tract interoception
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525643/
https://www.ncbi.nlm.nih.gov/pubmed/34464353
http://dx.doi.org/10.1172/jci.insight.152984
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