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Adipose-Derived Stem Cell-Derived Exosomes Inhibit Urethral Fibrosis Induced by Transforming Growth Factor β1 in Rats
Vol 37, Issue 2, 2023
Abstract
Background: Urethral stricture (US) is a common disease of the lower urinary tract in men caused by fibrosis. This study was designed to investigate the effect of adipose-derived stem cell (ADSC) exosomes (exos) and the possible mechanism on transforming growth factor β1 (TGF-β1)-induced urethral fibrosis in rats. Methods: ADSCs were isolated from adipose tissues from the inguinal region of three Sprague-Dawley (SD) rats and the expression of cell surface antigen markers CD90, CD105, and CD45 was detected by flow cytometry. Subsequently, ADSC-exos were isolated from third-passage ADSCs. The morphology, mean diameter, and expression of markers (CD63 and TSG101) of the ADSC-exos were observed by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting, respectively. After the construction of a rat model of urethral fibrosis (US) by the injection of 10 µg of TGF-β1, the effect of injecting ADSC-exos on urethral fibrosis was assessed. HE staining and Masson staining were used to observe the histopathological changes and degree of fibrosis in rat urethral tissues, respectively. The protein expression of Col III, α-SMA, fibronectin, TGF-β1, Smad3 (mothers against decapentaplegic homolog3), and p-Smad3 in urethral tissues was detected by western blotting. Results: After treatment of the US rat model with ADSC-exos, the mucosal injury of urethral tissues was ameliorated, the epithelium was well formed, and the degree of fibrosis was significantly reduced. Moreover, ADSC-exos significantly decreased the expression levels of fibrosis-related proteins (Col III, α-SMA, and fibronectin) and decreased the levels of TGF-β1, p-Smad3, and the p-Smad3/Smad3 ratio in the urethral tissues of US rats. Conclusions: ADSC-exos attenuate urethral fibrosis and inhibit the expression of fibrosis-related proteins in urethral tissues by inhibiting the TGF-β1/Smad3 signaling pathway in rats.
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Copyright (c) 2023 Tao Liang, Zheng-hao Dai, Hang Guo, Li-chang Zhong, Bin Zhang, Xiang Li, Wei-guo Chen
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Medical Genetics, University of Torino Medical School, Italy
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy