Escherichia coli Promotes Myofibroblast Differentiation in Urethral Fibrosis Urethral Stricture in vivo and vitro via regulating TGFβ/Smad Signaling Pathway

Urethral stricture in children is a challenging condition to treat, with a high rate of postoperative recurrence. Previous studies based on 16S rRNA and transcriptomic analyses have suggested a positive correlation between urethral stricture and Escherichia coli (E. coli), as well as the transforming growth factor-β (TGF-β)/Smad signaling pathway. Notably, even E. coli strains that do not cause typical urinary tract infection symptoms may still contribute to fibrotic stricture formation. In this study, we employed both in vitro cell culture and in vivo animal experiments to investigate the role of non-pathogenic E. coli in this process.Our results demonstrated that non-pathogenic E. coli promoted local production of TGF-β1 in urethral fibroblasts and rat urethral tissue, altered the ratio of transcription factors Smad2 and Smad3, and induced the release of inflammatory cytokines. This cascade facilitated the transformation of fibroblasts, ultimately leading to urethral stricture.We conclude that the presence of E. coli contributes to urethral fibrosis and stricture by promoting the release of inflammatory cytokines and activating the TGF-β1 signaling cascade, thereby enhancing the activation and proliferation of myofibroblasts responsible for scar formation. Modulation of the microbiota may represent a potential future direction for the prevention and treatment of urethral stricture.