Voiding defects in acute radiation cystitis driven by urothelial barrier defect through loss of E-cadherin, ZO-1 and Uroplakin III

Abstract Long term-side effects from cancer therapies are a growing health care concern as life expectancy among cancer survivors increases. Damage to the bladder is common in patients treated with radiation therapy for pelvic cancers and can result in radiation (hemorrhagic) cystitis (RC). The dise...

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Autores principales:	Bernadette M. M. Zwaans, Alexander L. Carabulea, Sarah N. Bartolone, Elijah P. Ward, Michael B. Chancellor, Laura E. Lamb
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/01a03e6fce3b4247a5fdee30c009dbef
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spelling	oai:doaj.org-article:01a03e6fce3b4247a5fdee30c009dbef2021-12-02T19:17:04ZVoiding defects in acute radiation cystitis driven by urothelial barrier defect through loss of E-cadherin, ZO-1 and Uroplakin III10.1038/s41598-021-98303-22045-2322https://doaj.org/article/01a03e6fce3b4247a5fdee30c009dbef2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98303-2https://doaj.org/toc/2045-2322Abstract Long term-side effects from cancer therapies are a growing health care concern as life expectancy among cancer survivors increases. Damage to the bladder is common in patients treated with radiation therapy for pelvic cancers and can result in radiation (hemorrhagic) cystitis (RC). The disease progression of RC consists of an acute and chronic phase, separated by a symptom-free period. Gaining insight in tissue changes associated with these phases is necessary to develop appropriate interventions. Using a mouse preclinical model, we have previously shown that fibrosis and vascular damage are the predominant pathological features of chronic RC. The goal of this study was to determine the pathological changes during acute RC. We identified that radiation treatment results in a temporary increase in micturition frequency and decrease in void volume 4–8 weeks after irradiation. Histologically, the micturition defect is associated with thinning of the urothelium, loss of urothelial cell–cell adhesion and tight junction proteins and decrease in uroplakin III expression. By 12 weeks, the urothelium had regenerated and micturition patterns were similar to littermate controls. No inflammation or fibrosis were detected in bladder tissues after irradiation. We conclude that functional bladder defects during acute RC are driven primarily by a urothelial defect.Bernadette M. M. ZwaansAlexander L. CarabuleaSarah N. BartoloneElijah P. WardMichael B. ChancellorLaura E. LambNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bernadette M. M. Zwaans Alexander L. Carabulea Sarah N. Bartolone Elijah P. Ward Michael B. Chancellor Laura E. Lamb Voiding defects in acute radiation cystitis driven by urothelial barrier defect through loss of E-cadherin, ZO-1 and Uroplakin III
description	Abstract Long term-side effects from cancer therapies are a growing health care concern as life expectancy among cancer survivors increases. Damage to the bladder is common in patients treated with radiation therapy for pelvic cancers and can result in radiation (hemorrhagic) cystitis (RC). The disease progression of RC consists of an acute and chronic phase, separated by a symptom-free period. Gaining insight in tissue changes associated with these phases is necessary to develop appropriate interventions. Using a mouse preclinical model, we have previously shown that fibrosis and vascular damage are the predominant pathological features of chronic RC. The goal of this study was to determine the pathological changes during acute RC. We identified that radiation treatment results in a temporary increase in micturition frequency and decrease in void volume 4–8 weeks after irradiation. Histologically, the micturition defect is associated with thinning of the urothelium, loss of urothelial cell–cell adhesion and tight junction proteins and decrease in uroplakin III expression. By 12 weeks, the urothelium had regenerated and micturition patterns were similar to littermate controls. No inflammation or fibrosis were detected in bladder tissues after irradiation. We conclude that functional bladder defects during acute RC are driven primarily by a urothelial defect.
format	article
author	Bernadette M. M. Zwaans Alexander L. Carabulea Sarah N. Bartolone Elijah P. Ward Michael B. Chancellor Laura E. Lamb
author_facet	Bernadette M. M. Zwaans Alexander L. Carabulea Sarah N. Bartolone Elijah P. Ward Michael B. Chancellor Laura E. Lamb
author_sort	Bernadette M. M. Zwaans
title	Voiding defects in acute radiation cystitis driven by urothelial barrier defect through loss of E-cadherin, ZO-1 and Uroplakin III
title_short	Voiding defects in acute radiation cystitis driven by urothelial barrier defect through loss of E-cadherin, ZO-1 and Uroplakin III
title_full	Voiding defects in acute radiation cystitis driven by urothelial barrier defect through loss of E-cadherin, ZO-1 and Uroplakin III
title_fullStr	Voiding defects in acute radiation cystitis driven by urothelial barrier defect through loss of E-cadherin, ZO-1 and Uroplakin III
title_full_unstemmed	Voiding defects in acute radiation cystitis driven by urothelial barrier defect through loss of E-cadherin, ZO-1 and Uroplakin III
title_sort	voiding defects in acute radiation cystitis driven by urothelial barrier defect through loss of e-cadherin, zo-1 and uroplakin iii
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/01a03e6fce3b4247a5fdee30c009dbef
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Voiding defects in acute radiation cystitis driven by urothelial barrier defect through loss of E-cadherin, ZO-1 and Uroplakin III

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