Quantification of the TGF- β/SMAD fibrosis pathway in bladder wall samples from children with congenital lower urinary tract anomalies
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...
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Elsevier
2023-03-01
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| Series: | Continence |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772973723000012 |
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| author | B. Xie N. Johal M. Millar C. Thrasivoulou A.J. Kanai A. Ahmed C.H. Fry |
| author_facet | B. Xie N. Johal M. Millar C. Thrasivoulou A.J. Kanai A. Ahmed C.H. Fry |
| author_sort | B. Xie |
| collection | DOAJ |
| description | 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. |
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| id | doaj.art-f8812b8218694b03b81e4b5375ed7662 |
| institution | Directory Open Access Journal |
| issn | 2772-9737 |
| language | English |
| last_indexed | 2024-04-09T23:38:57Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Continence |
| spelling | doaj.art-f8812b8218694b03b81e4b5375ed76622023-03-20T04:05:19ZengElsevierContinence2772-97372023-03-015100573Quantification of the TGF- β/SMAD fibrosis pathway in bladder wall samples from children with congenital lower urinary tract anomaliesB. Xie0N. Johal1M. Millar2C. Thrasivoulou3A.J. Kanai4A. Ahmed5C.H. Fry6School of Physiology, Pharmacology and Neuroscience, University of Bristol, UKDepartment of Urology, Great Ormond St Hospital, London, UKQueen’s Medical Research Institute, University of Edinburgh, UKDepartment of Cell and Developmental Biology, UCL, UKDepartments of Medicine, Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, USADepartment of Cell and Developmental Biology, UCL, UKSchool of Physiology, Pharmacology and Neuroscience, University of Bristol, UK; Correspondence to: School of Physiology, Pharmacology and Neuroscience, University Walk, University of Bristol, BS8 1TD, UK.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.http://www.sciencedirect.com/science/article/pii/S2772973723000012BladderCongenital anomalyFibrosisTGF-β pathwayImmunofluorescence labelling |
| spellingShingle | B. Xie N. Johal M. Millar C. Thrasivoulou A.J. Kanai A. Ahmed C.H. Fry Quantification of the TGF- β/SMAD fibrosis pathway in bladder wall samples from children with congenital lower urinary tract anomalies Continence Bladder Congenital anomaly Fibrosis TGF-β pathway Immunofluorescence labelling |
| title | Quantification of the TGF- β/SMAD fibrosis pathway in bladder wall samples from children with congenital lower urinary tract anomalies |
| title_full | Quantification of the TGF- β/SMAD fibrosis pathway in bladder wall samples from children with congenital lower urinary tract anomalies |
| title_fullStr | Quantification of the TGF- β/SMAD fibrosis pathway in bladder wall samples from children with congenital lower urinary tract anomalies |
| title_full_unstemmed | Quantification of the TGF- β/SMAD fibrosis pathway in bladder wall samples from children with congenital lower urinary tract anomalies |
| title_short | Quantification of the TGF- β/SMAD fibrosis pathway in bladder wall samples from children with congenital lower urinary tract anomalies |
| title_sort | quantification of the tgf β smad fibrosis pathway in bladder wall samples from children with congenital lower urinary tract anomalies |
| topic | Bladder Congenital anomaly Fibrosis TGF-β pathway Immunofluorescence labelling |
| url | http://www.sciencedirect.com/science/article/pii/S2772973723000012 |
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