Adaptive mechanisms in no flow vs. low flow ischemia in equine jejunum epithelium: Different paths to the same destination.
Authors: Dengler Franziska, Sternberg Felix, Grages Marei, Kästner Sabine Br, Verhaar Nicole
Journal: Frontiers in veterinary science
Summary
# Editorial Summary: Adaptive Mechanisms in Equine Intestinal Ischemia-Reperfusion Injury Intestinal ischaemia-reperfusion injury (IRI) represents a major complication in equine colic cases, yet the specific cellular survival mechanisms remain incompletely characterised. Dengler and colleagues investigated how equine jejunal epithelial tissue adapts to both complete (no flow) and partial (low flow) ischaemia by examining activation of four key adaptive pathways: hypoxia-inducible factor 1-alpha (HIF1α), AMP-activated protein kinase (AMPK), nuclear factor-erythroid 2-related factor 2 (NRF2), and autophagy. Their in vivo model revealed HIF1α activation occurred in both ischaemia types, whilst AMPK phosphorylation showed a tendency to increase during ischaemic periods; critically, increased LC3B expression combined with reduced mitochondrial gene expression indicated that mitophagy (selective autophagy of damaged mitochondria) was upregulated, potentially protecting cells from mitochondrial reactive oxygen species before they could cause epithelial damage. Interestingly, reactive oxygen species levels only briefly spiked following low flow ischaemia despite robust antioxidative responses, suggesting the intestinal epithelium possesses effective protective mechanisms independent of classical NRF2 signalling. For equine practitioners, these findings highlight that cellular survival following intestinal ischaemia involves multiple simultaneous adaptive pathways rather than a single dominant mechanism, and warrant further investigation into mitophagy as a potential therapeutic target in colic management.
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Practical Takeaways
- •Understanding that equine intestinal epithelium activates multiple protective mechanisms during ischemia (HIF1α, AMPK, mitophagy) may guide future therapeutic strategies to enhance survival during colic events
- •Mitophagy emerges as a potentially important protective pathway in equine intestinal IRI—future therapies targeting mitochondrial quality control could improve outcomes in colic cases with compromised blood flow
- •The finding that these adaptive mechanisms activate regardless of ischemia type (no-flow vs. low-flow) suggests interventions boosting these pathways may benefit diverse colic presentations
Key Findings
- •HIF1α activation occurred in both no-flow and low-flow ischemia models, indicating a key adaptive response to intestinal ischemia
- •Mitophagy (selective autophagy of mitochondria) was increased during IRI, likely protecting epithelial cells from mitochondria-derived reactive oxygen species
- •AMPK phosphorylation showed a tendency to increase during ischemia, supporting cellular energy adaptation mechanisms
- •ROS levels increased only briefly after low-flow ischemia onset, suggesting activation of antioxidative defense mechanisms independent of NRF2 activation