Mitogen-activated kinase pathway activation in epidermal lamellae in the acute stages of carbohydrate overload laminitis models and the effect of regional deep hypothermia on signalling pathways.
Authors: Gardner A K, Kelly C S, van Eps A W, Burns T A, Watts M R, Belknap J K
Journal: Equine veterinary journal
Summary
# Editorial Summary This investigation examined mitogen-activated protein kinase (MAPK) signalling in lamellae during the acute phase of carbohydrate overload-induced laminitis, using archived tissue from two experimental models and assessing whether regional deep hypothermia (RDH) modulated these inflammatory pathways. Two MAPK variants showed significant activation during early laminitis onset: phosphorylated ERK 1/2 and SAPK/JNK 1/2 concentrations increased substantially in lamellar tissue at the point of Obel Grade 1 lameness compared to controls, whereas p38 MAPK showed no meaningful change across any timepoint or treatment. Intriguingly, RDH application reduced ERK 1/2 phosphorylation to control levels, yet paradoxically increased SAPK/JNK 1/2 activation in cooled limbs—suggesting these two signalling cascades may operate independently and respond differently to therapeutic intervention. These findings tentatively support ERK 1/2 and SAPK/JNK 1/2 as potential therapeutic targets in laminitis management, though the counterintuitive effect of cooling on JNK pathway indicates that manipulating these pathways separately from RDH merits further investigation before any clinical application.
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Practical Takeaways
- •ERK 1/2 and SAPK/JNK signalling activation occurs in early laminitis and may represent therapeutic targets distinct from current cooling protocols
- •Regional deep hypothermia's effects on different MAPK pathways differ—it reduces SAPK/JNK but not ERK 1/2—suggesting future treatments might need to target multiple pathways independently
- •Early intervention targeting these specific signalling proteins may offer new approaches to mitigating lamellar injury during acute laminitis episodes
Key Findings
- •Lamellar samples showed statistically significant increased concentrations of activated ERK 1/2 at onset of Obel Grade 1 laminitis compared to control in the starch gruel model
- •Phospho-SAPK/JNK 1/2 exhibited significant increase in OG1 samples and was also increased in hypothermic versus ambient temperature limbs
- •No statistically significant changes in lamellar p38 MAPK concentrations were observed across any treatment groups
- •Regional deep hypothermia did not reduce ERK 1/2 activation despite reducing SAPK/JNK 1/2, suggesting independent therapeutic manipulation of these pathways may be possible