The mRNA-binding protein IGF2BP1 maintains intestinal barrier function by up-regulating occludin expression

Area of Science:

• Gastroenterology
• Molecular Biology
• Cell Biology

Background:

• Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) exhibits oncofetal expression and is present in intestinal tissue.
• Its role in intestinal homeostasis and barrier function remains largely unexplored.

Purpose of the Study:

• To investigate the function of IGF2BP1 in the adult intestinal epithelium.
• To determine the impact of IGF2BP1 ablation on intestinal homeostasis and barrier integrity.

Main Methods:

• Generation of Villin CreERT2:Igf2bp1flox/flox mice for conditional knockout of IGF2BP1 in intestinal epithelial cells (IECs).
• Assessment of gut barrier function, epithelial permeability, and inflammatory markers.
• Biochemical analyses, including mRNA-protein interaction studies and assessment of tight junction protein expression.

Main Results:

• IGF2BP1 ablation in adult mice induced mild active colitis and enteritis.
• IGF2BP1 deficiency exacerbated dextran sodium sulfate-induced colitis.
• Loss of IGF2BP1 compromised intestinal epithelial barrier function due to altered tight junction protein expression, specifically occludin.
• IGF2BP1 directly interacts with and stabilizes occludin mRNA, promoting its expression in IECs.

Conclusions:

• IGF2BP1 plays a vital role in maintaining intestinal barrier function.
• IGF2BP1-mediated regulation of occludin expression is a key mechanism for preventing colitis.
• Targeting IGF2BP1 could offer therapeutic potential for inflammatory bowel diseases.