Escherichia coli promotes myofibroblast differentiation in urethral fibrosis urethral stricture in vivo and vitro via regulating TGFβ/Smad signaling pathway.

OBJECTIVE: Urethral stricture in children remains a challenging condition, with a high rate of postoperative recurrence. Previous studies employing 16 S rRNA sequencing and transcriptomic analyses have identified a positive association between urethral stricture, Escherichia coli (E. coli), and activation of the transforming growth factor-β (TGF-β)/Smad signaling pathway. Notably, even E. coli strains that do not cause overt urinary tract infection symptoms may contribute to fibrotic stricture formation.

METHODS: In this study, we employed both in vitro cell culture and in vivo animal models to investigate the role of non-pathogenic E. coli in urethral fibrosis.

RESULTS: Our results demonstrated that non-pathogenic E. coli promoted local TGF-β1 production in urethral fibroblasts (UFs) and rat urethral tissues, modulated the expression of downstream signaling mediators Smad2 and Smad3, and induced the release of pro-inflammatory cytokines. This cascade facilitated myofibroblast differentiation, ultimately contributing to urethral fibrosis and stricture formation.

CONCLUSION: These findings suggest that E. coli colonization promotes urethral fibrosis by stimulating inflammatory cytokine release and activating the TGF-β1/Smad signaling pathway, thereby driving myofibroblast activation and excessive extracellular matrix deposition. Modulation of the urethral microbiota warrants further investigation as a potential strategy for the prevention and management of urethral stricture.