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Contractile and structural properties of detrusor from children with neurogenic lower urinary tract dysfunction

Research output: Contribution to journalArticlepeer-review

Navroop Johal, Kevin X. Cao, Boyu Xie, Michael Millar, Reena Davda, Aamir Ahmed, Anthony J. Kanai, Dan N. Wood, Rita I. Jabr, Christopher H. Fry

Original languageEnglish
Article number863
JournalBiology
Volume10
Issue number9
DOIs
PublishedSep 2021

Bibliographical note

Funding Information: The support for this project was provided by Liverpool Children?s Foundation to NJ, The Urology Foundation and The Royal College of Surgeons of England to KC and CHF, the National Institute of Health (R01 DK098361-06) to AJK and CHF. Funding Information: Funding: The support for this project was provided by Liverpool Children’s Foundation to NJ, The Urology Foundation and The Royal College of Surgeons of England to KC and CHF, the National Institute of Health (R01 DK098361-06) to AJK and CHF. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

Abstract

Neurogenic lower urinary tract (NLUT) dysfunction in paediatric patients can arise after congenital or acquired conditions that affect bladder innervation. With some patients, urinary tract dysfunction remains and is more difficult to treat without understanding the pathophysiology. We measured in vitro detrusor smooth muscle function of samples from such bladders and any association with altered Wnt-signalling pathways that contribute to both foetal development and connective tissue deposition. A comparator group was tissue from children with normally functioning bladders. Nerve-mediated and agonist-induced contractile responses and passive stiffness were measured. Histology measured smooth muscle and connective tissue proportions, and multiplex immunohisto-chemistry recorded expression of protein targets associated with Wnt-signalling pathways. Detrusor from the NLUT group had reduced contractility and greater stiffness, associated with increased connective tissue content. Immunohistochemistry showed no major changes to Wnt-signalling com-ponents except down-regulation of c-Myc, a multifunctional regulator of gene transcription. NLUT is a diverse term for several diagnoses that disrupt bladder innervation. While we cannot speculate about the reasons for these pathophysiological changes, their recognition should guide research to understand their ultimate causes and develop strategies to attenuate and even reverse them. The role of changes to the Wnt-signalling pathways was minor.

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