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      A novel trauma induced urethral stricture in rat model

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          Abstract

          Urethral stricture (US) is a longstanding disease, while there has not existed a suitable animal model to mimic the condition. We aimed to establish a trauma-induced US animal model to simulate this clinical scenario. A total of 30 rats were equally distributed into two groups, sham and US group. All rats were anesthetized with isoflurane and undergone cystostomy. In the US group, a 2 mm incision was made in the urethra and sutured to induce US. The sham group only make a skin incision on the ventral side of the anterior urethra. 4 weeks later, ultrasound and cystourethrography were performed to evaluate the degree of urethral stricture, pathological examinations were carried out to evaluate the degree of fibrosis. Urodynamic evaluation and mechanical tissue testing were performed to evaluate the bladder function and urethral tissue stiffness. The results showed that the urethral mucosa was disrupted and urethral lumen was stenosed in the US group. Additionally, the US group showed elevated bladder pressure, prolonged micturition intervals and increased tissue stiffness. In conclusion, the rat urethral stricture model induced by trauma provides a closer representation of the real clinical scenario. This model will significantly contribute to advancing research on the mechanisms underlying traumatic urethral stricture.

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          Most cited references31

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          The stiffness of living tissues and its implications for tissue engineering

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            YAP/TAZ Are Mechanoregulators of TGF-β-Smad Signaling and Renal Fibrogenesis.

            Like many organs, the kidney stiffens after injury, a process that is increasingly recognized as an important driver of fibrogenesis. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are related mechanosensory proteins that bind to Smad transcription factors, the canonical mediators of profibrotic TGF-β responses. Here, we investigated the role of YAP/TAZ in the matrix stiffness dependence of fibroblast responses to TGF-β. In contrast to growth on a stiff surface, fibroblast growth on a soft matrix led to YAP/TAZ sequestration in the cytosol and impaired TGF-β-induced Smad2/3 nuclear accumulation and transcriptional activity. YAP knockdown or treatment with verteporfin, a drug that was recently identified as a potent YAP inhibitor, elicited similar changes. Furthermore, verteporfin reduced YAP/TAZ levels and decreased the total cellular levels of Smad2/3 after TGF-β stimulation. Verteporfin treatment of mice subjected to unilateral ureteral obstruction similarly reduced YAP/TAZ levels and nuclear Smad accumulation in the kidney, and attenuated renal fibrosis. Our data suggest that organ stiffening cooperates with TGF-β to induce fibrosis in a YAP/TAZ- and Smad2/3-dependent manner. Interference with this YAP/TAZ and TGF-β/Smad crosstalk likely underlies the antifibrotic activity of verteporfin. Finally, through repurposing of a clinically used drug, we illustrate the therapeutic potential of a novel mechanointerference strategy that blocks TGF-β signaling and renal fibrogenesis.
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              Male Urethral Stricture: American Urological Association Guideline.

              The purpose of this Guideline is to provide a clinical framework for the diagnosis and treatment of male urethral stricture.
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                Author and article information

                Contributors
                zzhalways2@163.com
                tanshuo@csu.edu.cn
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                15 March 2024
                15 March 2024
                2024
                : 14
                : 6325
                Affiliations
                [1 ]GRID grid.452223.0, ISNI 0000 0004 1757 7615, Department of Urology, , Xiangya Hospital of Central South University, ; Changsha, People’s Republic of China
                [2 ]Department of Urology, Third Xiangya Hospital of Central South University, ( https://ror.org/05akvb491) Changsha, People’s Republic of China
                [3 ]Provincial Laboratory for Diagnosis and Treatment of Genitourinary System Disease, Changsha, People’s Republic of China
                Author information
                http://orcid.org/0000-0002-5567-3312
                Article
                55408
                10.1038/s41598-024-55408-8
                10943079
                38491041
                16304586-bb32-40bf-b422-4e540dba7d92
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 2 November 2023
                : 22 February 2024
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 82170706
                Award Recipient :
                Funded by: Central South University Independent Exploration and Innovation Project for Graduate Students, and Graduate Innovation Project of Hunan Province
                Award ID: CX20230279
                Award Recipient :
                Categories
                Article
                Custom metadata
                © Springer Nature Limited 2024

                Uncategorized
                urethral stricture,rat model,cystostomy,cystometry,urethral fibrosis,urology,trauma,urogenital diseases

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