Cargando…

Formation of Double Stranded RNA Provokes Smooth Muscle Contractions and Structural Modifications in Bladder Ischemia

PURPOSE: Growing evidence suggests that ischemia provokes detrusor overactivity and degenerative responses in the bladder. Underlying mechanisms appear to involve modification of smooth muscle contractile rudiments by hypoxia, redox, cellular stress and cell survival signaling. Downstream pathways o...

Descripción completa

Detalles Bibliográficos
Autores principales: Yang, Jing-Hua, Zhao, Zuohui, Niu, Wanting, Choi, Han-Pil, Azadzoi, Kazem M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9676006/
https://www.ncbi.nlm.nih.gov/pubmed/36415310
http://dx.doi.org/10.2147/RRU.S388464
_version_ 1784833496592678912
author Yang, Jing-Hua
Zhao, Zuohui
Niu, Wanting
Choi, Han-Pil
Azadzoi, Kazem M
author_facet Yang, Jing-Hua
Zhao, Zuohui
Niu, Wanting
Choi, Han-Pil
Azadzoi, Kazem M
author_sort Yang, Jing-Hua
collection PubMed
description PURPOSE: Growing evidence suggests that ischemia provokes detrusor overactivity and degenerative responses in the bladder. Underlying mechanisms appear to involve modification of smooth muscle contractile rudiments by hypoxia, redox, cellular stress and cell survival signaling. Downstream pathways of cellular stress and stress response molecules eliciting bladder dysfunction in ischemia remain largely elusive. Our goal was to define the role of double stranded RNA (dsRNA), a stress response molecule provoked by redox, in ischemia mediated bladder dysfunction. METHODS: A rat model of pelvic ischemia along with a cell culture hypoxia model were used to investigate the expression levels, functional consequences, structural aspects, and regulatory mechanisms of dsRNA in the bladder. Gene and protein expression were examined by reverse transcription polymerase chain reaction (RT-PCR), dot blot, and Western blotting, respectively. Tissue structure and function were assessed using histological staining and organ bath. Regulatory mechanisms were analyzed in cultured bladder smooth muscle cells. RESULTS: The data presented here provide the first evidence of the formation of dsRNA in the overactive bladder. dsRNA is a cellular stress response molecule that sensitizes smooth muscle and regulates inflammatory and degenerative rejoinders. Our data suggest that the production of dsRNA in the bladder is provoked by ischemia. Formation of dsRNA appears to augment bladder smooth muscle contractions and provoke fibrotic and apoptotic responses. Downstream actions of dsRNA in the bladder may involve upregulation of dsRNA-activated protein kinase R (PKR) and caspase-3, the executioner of apoptosis. CONCLUSION: Activation of dsRNA/PKR pathway may play a role in sensitization of bladder smooth muscle cells to contractile stimuli, whereas dsRNA and caspase-3 crosstalk appear to modulate cellular stress and instigate degenerative responses in bladder ischemia. These observations suggest the role of dsRNA in bladder dysfunction and may open new perspectives to overcome overactive smooth muscle contractions and structural damage in the bladder.
format Online
Article
Text
id pubmed-9676006
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Dove
record_format MEDLINE/PubMed
spelling pubmed-96760062022-11-21 Formation of Double Stranded RNA Provokes Smooth Muscle Contractions and Structural Modifications in Bladder Ischemia Yang, Jing-Hua Zhao, Zuohui Niu, Wanting Choi, Han-Pil Azadzoi, Kazem M Res Rep Urol Original Research PURPOSE: Growing evidence suggests that ischemia provokes detrusor overactivity and degenerative responses in the bladder. Underlying mechanisms appear to involve modification of smooth muscle contractile rudiments by hypoxia, redox, cellular stress and cell survival signaling. Downstream pathways of cellular stress and stress response molecules eliciting bladder dysfunction in ischemia remain largely elusive. Our goal was to define the role of double stranded RNA (dsRNA), a stress response molecule provoked by redox, in ischemia mediated bladder dysfunction. METHODS: A rat model of pelvic ischemia along with a cell culture hypoxia model were used to investigate the expression levels, functional consequences, structural aspects, and regulatory mechanisms of dsRNA in the bladder. Gene and protein expression were examined by reverse transcription polymerase chain reaction (RT-PCR), dot blot, and Western blotting, respectively. Tissue structure and function were assessed using histological staining and organ bath. Regulatory mechanisms were analyzed in cultured bladder smooth muscle cells. RESULTS: The data presented here provide the first evidence of the formation of dsRNA in the overactive bladder. dsRNA is a cellular stress response molecule that sensitizes smooth muscle and regulates inflammatory and degenerative rejoinders. Our data suggest that the production of dsRNA in the bladder is provoked by ischemia. Formation of dsRNA appears to augment bladder smooth muscle contractions and provoke fibrotic and apoptotic responses. Downstream actions of dsRNA in the bladder may involve upregulation of dsRNA-activated protein kinase R (PKR) and caspase-3, the executioner of apoptosis. CONCLUSION: Activation of dsRNA/PKR pathway may play a role in sensitization of bladder smooth muscle cells to contractile stimuli, whereas dsRNA and caspase-3 crosstalk appear to modulate cellular stress and instigate degenerative responses in bladder ischemia. These observations suggest the role of dsRNA in bladder dysfunction and may open new perspectives to overcome overactive smooth muscle contractions and structural damage in the bladder. Dove 2022-11-16 /pmc/articles/PMC9676006/ /pubmed/36415310 http://dx.doi.org/10.2147/RRU.S388464 Text en © 2022 Yang et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Yang, Jing-Hua
Zhao, Zuohui
Niu, Wanting
Choi, Han-Pil
Azadzoi, Kazem M
Formation of Double Stranded RNA Provokes Smooth Muscle Contractions and Structural Modifications in Bladder Ischemia
title Formation of Double Stranded RNA Provokes Smooth Muscle Contractions and Structural Modifications in Bladder Ischemia
title_full Formation of Double Stranded RNA Provokes Smooth Muscle Contractions and Structural Modifications in Bladder Ischemia
title_fullStr Formation of Double Stranded RNA Provokes Smooth Muscle Contractions and Structural Modifications in Bladder Ischemia
title_full_unstemmed Formation of Double Stranded RNA Provokes Smooth Muscle Contractions and Structural Modifications in Bladder Ischemia
title_short Formation of Double Stranded RNA Provokes Smooth Muscle Contractions and Structural Modifications in Bladder Ischemia
title_sort formation of double stranded rna provokes smooth muscle contractions and structural modifications in bladder ischemia
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9676006/
https://www.ncbi.nlm.nih.gov/pubmed/36415310
http://dx.doi.org/10.2147/RRU.S388464
work_keys_str_mv AT yangjinghua formationofdoublestrandedrnaprovokessmoothmusclecontractionsandstructuralmodificationsinbladderischemia
AT zhaozuohui formationofdoublestrandedrnaprovokessmoothmusclecontractionsandstructuralmodificationsinbladderischemia
AT niuwanting formationofdoublestrandedrnaprovokessmoothmusclecontractionsandstructuralmodificationsinbladderischemia
AT choihanpil formationofdoublestrandedrnaprovokessmoothmusclecontractionsandstructuralmodificationsinbladderischemia
AT azadzoikazemm formationofdoublestrandedrnaprovokessmoothmusclecontractionsandstructuralmodificationsinbladderischemia