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

objectiveUrethral 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.

methodsIn 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.

resultsOur 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.

conclusionThese 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.