An Innovative Animal Model for Urethral Fibrosis in Male Rats and the Restorative Effects of a Novel TGF-β–Modulating Regenerative Molecule: Correlative Histopathology and Immunostaining Analysis
نویسندگان
1 Faculty of Veterinary Medicine, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
2 Faculty of Veterinary Medicine, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
3 Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
4 Faculty of Veterinary Medicine, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
5 Department of Anatomy, Faculty of Medicine, Tehran Azad University of Medical Sciences, Tehran, Iran
6 Department of Urology, Mellannie Nutrition Research Institute, Manchester, UK
doi
10.22034/tru.2026.572369.1319چکیده
Introduction: Urethral fibrosis is the main pathological substrate of urethral stricture disease and remains therapeutically challenging due to limited regenerative options. Robust and reproducible animal models are essential for translational research. This study aimed to establish a standardized and reproducible animal model of urethral fibrosis in male rats and to evaluate the therapeutic efficacy of a novel, clearly defined regenerative molecule that modulates fibrotic signaling pathways. Methods: Eighty adult male Sprague–Dawley rats were randomly assigned to four groups: Sham, Fibrosis Control, Low-Dose Treatment, and High-Dose Treatment. Urethral fibrosis was induced using a controlled circumferential electrocautery injury. The regenerative molecule, defined as a synthetic small-molecule modulator of the TGF-β1/SMAD pathway with anti-fibrotic properties, was administered intraperitoneally for 21 days. Outcomes included histopathological fibrosis scoring, collagen quantification, and immunohistochemical analysis of α-SMA and TGF-β1. Results: The fibrosis model demonstrated high reproducibility with consistent pathological changes. Treatment significantly reduced fibrosis severity, collagen deposition, and expression of α-SMA and TGF-β1 in a dose-dependent manner (P-value<0.001). Conclusion: This study introduces a reliable rat model of urethral fibrosis and demonstrates that targeted modulation of TGF-β signaling can effectively attenuate fibrotic remodeling, supporting future translational research.
