The PVT1/miR-216a-5p/TLR4 Signaling Axis Regulates the Inflammation and Intestinal Epithelial Barrier Function of...

Area of Science:

• Gastroenterology
• Molecular Biology
• Immunology

Background:

• Ulcerative colitis (UC) is a chronic inflammatory bowel disease with significant patient burden.
• Understanding the molecular mechanisms underlying UC pathogenesis is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the role of the PVT1/miR-216a-5p/TLR4 signaling axis in ulcerative colitis.
• To evaluate the impact of this axis on intestinal inflammation and epithelial barrier function.

Main Methods:

• Established in vitro (LPS-stimulated RAW264.7 and Caco-2 co-culture) and in vivo (DSS-induced colitis in mice) models.
• Assessed cell cytotoxicity, barrier function (TEER, ZO-1, occludin), pro-inflammatory cytokine levels (ELISA), and gene/protein expression (RT-qPCR, Western blot).
• Verified targeting relationships using dual-luciferase reporter assays.

Main Results:

• PVT1 and TLR4 levels were elevated, while miR-216a-5p was decreased in UC models.
• Increased inflammation, cytotoxicity, and disrupted barrier function were observed.
• PVT1 inhibition reversed UC-associated changes; miR-216a-5p inhibition counteracted PVT1 knockdown effects.

Conclusions:

• The PVT1/miR-216a-5p/TLR4 axis plays a significant role in UC pathogenesis.
• This signaling pathway influences intestinal inflammation and epithelial barrier integrity.
• The PVT1/miR-216a-5p axis represents a potential therapeutic target for ulcerative colitis.