Adenosine A2B receptor modulates intestinal barrier function under hypoxic and ischemia/reperfusion conditions

Area of Science:

• Gastroenterology
• Immunology
• Physiology

Background:

• Intestinal barrier dysfunction following ischemia/reperfusion (I/R) and hypoxia contributes to inflammation.
• The Adenosine A2B receptor (A2BAR) role in regulating intestinal barrier function under these conditions was investigated.

Purpose of the Study:

• To elucidate the role of A2BAR in maintaining intestinal barrier function during I/R and acute hypoxia.
• To evaluate the therapeutic potential of A2BAR antagonism in preserving intestinal barrier integrity.

Main Methods:

• Utilized a mouse model of intestinal I/R and an in vitro epithelial cell culture model under hypoxia.
• Administered a specific A2BAR antagonist (PSB1115) to assess its effects on tight junction proteins (Claudin-1, occludin, ZO-1) and epithelial permeability (TER).
• Analyzed protein and RNA expression, immunohistochemistry, and transepithelial resistance.

Main Results:

• A2BAR antagonism with PSB1115 significantly increased tight junction protein expression in both I/R and hypoxia models.
• PSB1115 treatment attenuated the disruption of tight junction protein distribution.
• Inhibition of A2BAR prevented the decrease in transepithelial resistance, thereby maintaining intestinal barrier function.

Conclusions:

• Antagonism of A2BAR activity improves intestinal epithelial structure and barrier function in models of intestinal I/R and acute hypoxia.
• These findings highlight a potentially detrimental role of A2BAR in intestinal I/R and acute hypoxic conditions.
• Targeting A2BAR may represent a novel therapeutic strategy for inflammatory disorders associated with intestinal barrier dysfunction.