Related Experiment Video
Updated: Mar 28, 2026
Visualization of Neutrophil Extracellular Traps in Mesenteric Venules After Mesenteric Ischemia-Reperfusion Injury via Intravital Microscopy
Published on: September 27, 2024
The Receptor for Advanced Glycation Endproducts Does Not Contribute to Pathology in a Mouse Mesenteric
Mike C L Wu1, Timothy D Gilmour1, Susanna Mantovani1
1School of Biomedical Sciences, The University of Queensland , Brisbane, QLD , Australia.
Abstract:
The receptor for advanced glycation endproducts (RAGE) can engage a diverse class of ligands and contribute to the immune and inflammatory response to infection and injury. It is known to be a pathogenic receptor in many inflammatory diseases, including ischemia/reperfusion (IR) injuries in several tissues; however, its role has not been investigated in IR injuries of the intestine to date. Mesenteric (or intestinal) IR leads to recruitment of inflammatory cells into intestinal interstitial spaces, which markedly disrupts intestinal mucosa. IR-induced mucosal injury is accompanied by the development of a local and systemic inflammatory response and remote organ injury, and results in high mortality in the clinic. We hypothesized that elimination of RAGE signaling using RAGE(-/-) mice would result in decreased local and remote organ injury and reduced inflammation in a mesenteric IR model, and thus be a target for therapeutic intervention. We found that RAGE ligands including HMGB-1 and C3a were elevated after mesenteric IR indicating the potential for enhanced RAGE activation in this model. However despite this, wild-type and RAGE(-/-) mice both displayed similar degrees of mesenteric injury, neutrophil infiltration, intestinal edema, cytokine generation, neutrophil mobilization, and remote organ injury after mesenteric IR. We, therefore, conclude that despite its role in other organ IR injuries, and the robust production of RAGE ligands after intestinal ischemia, RAGE itself does not directly influence tissue injury and the inflammatory response in mesenteric IR.
Insights
Receptor for advanced glycation endproducts (RAGE) does not impact intestinal injury or inflammation following mesenteric ischemia/reperfusion. Studies show RAGE signaling is not a therapeutic target for this condition.
Area of Science:
- Inflammation and Immunology
- Gastroenterology
- Pathophysiology
Background:
- The receptor for advanced glycation endproducts (RAGE) is implicated in inflammatory diseases and injuries.
- Its role in intestinal ischemia/reperfusion (IR) injuries remains uninvestigated.
- Mesenteric IR causes significant mucosal damage, inflammation, and remote organ injury, leading to high mortality.
Purpose of the Study:
- To investigate the role of RAGE in mesenteric IR injuries.
- To determine if eliminating RAGE signaling reduces local and remote organ injury and inflammation.
- To assess RAGE as a potential therapeutic target for intestinal IR.
Main Methods:
- Utilized RAGE knockout (RAGE(-/-)) mice and wild-type littermates.
- Induced mesenteric IR injury.
- Assessed degrees of mesenteric injury, neutrophil infiltration, intestinal edema, cytokine generation, and remote organ injury.
Main Results:
- RAGE ligands (HMGB-1, C3a) were elevated post-mesenteric IR.
- No significant differences were observed in mesenteric injury, inflammation, or remote organ injury between RAGE(-/-) and wild-type mice.
- Neutrophil infiltration, edema, and cytokine levels were similar in both groups.
Conclusions:
- Despite elevated RAGE ligands, RAGE signaling does not directly influence tissue injury or inflammation in mesenteric IR.
- RAGE is not a direct therapeutic target for mitigating injury in mesenteric IR.
- Findings contrast with RAGE's known role in IR injuries in other tissues.
