Expression of Proteinase-Activated Receptor 2 During Colon Volvulus in the Horse.
Authors: Lambertini Carlotta, Zannoni Augusta, Romagnoli Noemi, Bombardi Cristiano, Morini Maria, Dondi Francesco, Bernardini Chiara, Forni Monica, Rinnovati Riccardo, Spadari Alessandro
Journal: Frontiers in veterinary science
Summary
# Editorial Summary: PAR2 Expression in Equine Large Colon Volvulus Large colon volvulus carries a particularly grim prognosis when ischaemic-reperfusion injury develops, yet the molecular mechanisms driving the secondary inflammatory cascade remain incompletely understood; this Italian research team investigated proteinase-activated receptor 2 (PAR2), a cell-surface receptor implicated in gastrointestinal inflammation, by comparing colonic tissue from eight horses undergoing emergency surgery for volvulus against healthy controls. Using immunofluorescence, western blotting and RT-qPCR on samples harvested from the pelvic flexure, they identified PAR2 localisation within enterocytes, intestinal glands and neurons of both submucosal and myenteric plexi, with notable evidence of PAR2 activation (demonstrated by a characteristic 25 kDa protein fragment alongside the expected 44 kDa band) in affected horses despite similar mRNA expression levels to controls. Concurrent gene expression profiling revealed significant upregulation of pro-inflammatory mediators—specifically CXCL1, IL-8 and MIP-2β—in the colic cohort, establishing a clear link between PAR2 activation and the inflammatory microenvironment of volvulus. These findings suggest PAR2 may serve as a therapeutic target for modulating the damaging inflammatory response in large colon volvulus, potentially improving outcomes when combined with surgical intervention; further research should explore whether PAR2 antagonists might reduce tissue damage during the critical post-operative period, particularly in cases with established ischaemic-reperfusion injury.
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Practical Takeaways
- •PAR2 activation appears to be a key driver of the inflammatory cascade in colon volvulus; understanding this mechanism may inform future anti-inflammatory treatment strategies beyond current supportive care
- •The upregulation of chemokines (CXCL1, IL-8, MIP-2β) confirms severe intestinal inflammation occurs during volvulus and may help explain poor prognosis outcomes in clinical cases
- •Early intervention and management of ischemic-reperfusion injury should target inflammatory pathways, as PAR2-mediated inflammation appears central to tissue damage
Key Findings
- •PAR2 protein was activated (detected as 25 kDa fragment) in colon tissue from volvulus horses despite similar mRNA levels to healthy controls
- •CXCL1, IL-8, and MIP-2β gene expression were significantly upregulated in volvulus cases compared to healthy horses
- •PAR2 immunostaining localized to enterocytes, intestinal glands, and neurons of submucosal and myenteric plexi
- •Three of eight surgical cases (37.5%) were euthanized due to clinical deterioration