STEAP4 Modulates Intestinal Barrier Dysfunction and Inflammatory Signaling Pathways in Ulcerative Colitis

Area of Science:

• Gastroenterology
• Immunology
• Molecular Biology

Background:

• Ulcerative colitis (UC) involves intestinal barrier dysfunction and chronic inflammation.
• The precise mechanisms driving UC pathogenesis are not fully understood.
• Six-transmembrane epithelial antigen of the prostate 4 (STEAP4), a metalloreductase involved in redox regulation, is a potential factor.

Purpose of the Study:

• To investigate the role of STEAP4 in the pathogenesis of ulcerative colitis.
• To explore STEAP4's impact on intestinal barrier integrity and inflammatory responses.

Main Methods:

• Analysis of clinical samples from IBD patients.
• Utilized a dextran sulfate sodium (DSS)-induced murine colitis model.
• Employed lipopolysaccharide (LPS)-treated intestinal epithelial cell lines (NCM460, HT-29).
• Performed H&E staining, Western blot, and siRNA-mediated STEAP4 knockdown.

Main Results:

• STEAP4 expression was significantly elevated in inflamed mucosa from human, murine, and in vitro models.
• STEAP4 knockdown restored tight junction protein claudin-1, increased TEER, and decreased permeability.
• STEAP4 suppression attenuated LPS-induced pro-inflammatory cytokines (TNF-α, IL-6) by inhibiting NF-κB phosphorylation.

Conclusions:

• STEAP4 is a critical regulator of mucosal inflammation in UC.
• STEAP4 links redox homeostasis, epithelial barrier function, and NF-κB signaling.
• STEAP4 represents a potential therapeutic target for restoring intestinal homeostasis in UC.