Ulcerative colitis (UC) is characterized by intestinal barrier dysfunction and chronic inflammation, yet its underlying mechanisms remain incompletely understood. This study investigates the role of Six-transmembrane epithelial antigen of the prostate 4 (STEAP4), a metalloreductase linked to redox regulation, in UC pathogenesis. Using clinical samples from IBD patients, a dextran sulfate sodium (DSS)-induced murine colitis model, and lipopolysaccharide (LPS)-treated intestinal epithelial cells (NCM460 and HT-29), we demonstrated that STEAP4 expression was significantly upregulated in inflamed mucosa across human, murine, and in vitro models. H n=3), increased TEER value (p < 0.001; n=3), decreased the permeability of FITC‐D (p < 0.01, p < 0.001; n=3) and suppressed LPS-induced pro-inflammatory cytokines (TNF-α, IL-6) (p < 0.05; n=3) by attenuating NF-κB phosphorylation (p65, IκBα) (p < 0.05, p < 0.01, p < 0.001; n=3). These findings position STEAP4 as a critical regulator of mucosal inflammation, bridging redox homeostasis, epithelial barrier function, and NF-κB-driven immune responses. Our study highlights STEAP4 as a potential therapeutic target for restoring intestinal homeostasis in UC, warranting further exploration of its molecular interactions and translational applications.
Xu et al. (Mon,) studied this question.