Targeting immunoproteasome and glutamine supplementation prevent intestinal hyperpermeability

Area of Science:

• Gastroenterology
• Immunology
• Molecular Biology

Background:

• Intestinal hyperpermeability is linked to various disorders.
• The role of the ubiquitin proteasome system in gut barrier regulation requires further investigation.

Purpose of the Study:

• To explore the ubiquitin proteasome system's involvement in gut barrier function.
• To assess the impact of proteasome inhibition and glutamine supplementation on intestinal permeability in stress and post-inflammatory mouse models.

Main Methods:

• Utilized water avoidance stress (WAS) and post-TNBS inflammatory mouse models.
• Administered selective proteasome inhibitors and employed β2i proteasome subunit knockout mice.
• Evaluated the effects of glutamine supplementation.

Main Results:

• Both WAS and post-TNBS models showed increased proteasome activity and expression ratio, correlating with higher intestinal permeability.
• Proteasome inhibition significantly reduced intestinal hyperpermeability in both models.
• β2i subunit knockout mice displayed reduced intestinal permeability during WAS, and glutamine supplementation improved colonic permeability.

Conclusions:

• The proteasome system is dysregulated in the colonic mucosa under stress and inflammatory conditions.
• Targeting the immunoproteasome system effectively mitigates associated intestinal hyperpermeability.
• Glutamine supplementation offers a potential therapeutic strategy for improving gut barrier function.