Xie, B;
Johal, N;
Millar, M;
Thrasivoulou, C;
Kanai, AJ;
Ahmed, A;
Fry, CH;
(2023)
Quantification of the TGF- β/SMAD fibrosis pathway in bladder wall samples from children with congenital lower urinary tract anomalies.
Continence
, 5
10.1016/j.cont.2023.100573.
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Abstract
Replacement of detrusor smooth muscle (SM) with connective tissue (CT) in the bladder wall has functional consequences to lower urinary tract function, namely changes to the filling compliance and its contractile performance. In children with congenital anomalies such tissue remodelling may underlie the poor prognosis that is characteristic of a significant proportion of these patients. We have quantified the extent of CT deposition in bladder tissue samples from four age-matched (24–72 months) patient groups, namely: normally-functioning (control) bladders; bladder exstrophy, neurogenic bladders (NGB) and posterior urethral valves (PUV). In addition, using multiplex labelling we have also quantified, in neighbouring sections, expression of TGF-β, a downstream transcription factor SMAD2, connexin-43, as well as DAPI labelling of nuclear material, separately in the SM and CT regions of the detrusor layer. TGF-β receptor (TGF-βR) and Cx43 labelling were greater in SM regions of exstrophy and NGB (but not PUV) tissues when compared to control, were but unchanged in CT regions. SMAD2 labelling was similar in all groups in both SM and CT regions, with minor increases in exstrophy, NGB and PUV SM regions and small reductions in exstrophy and NGB CT regions. DAPI staining was less in CT compared with SM regions but was unchanged between patient groups. Overall, the TGF-β pathway shows variability of expression in congenital bladder anomalies, compared with control tissue, that at this period of post-natal development is greater in the extant SM layer. Antifibrotic strategies that target this pathway offer an approach to minimise fibrotic development.
| Type: | Article |
|---|---|
| Title: | Quantification of the TGF- β/SMAD fibrosis pathway in bladder wall samples from children with congenital lower urinary tract anomalies |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.cont.2023.100573 |
| Language: | English |
| Additional information: | © 2023 The Author(s). Published by Elsevier B.V. on behalf of International Continence Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10179565 |
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