An investigation of the equine epidermal growth factor system during hyperinsulinemic laminitis.
Authors: de Laat Melody A, Spence Robert J, Sillence Martin N, Pollitt Christopher C
Journal: PloS one
Summary
# Editorial Summary Hyperinsulinaemic laminitis remains a major clinical concern in equine practice, yet the underlying cellular mechanisms driving epidermal proliferation and lamellar failure are not fully understood. De Laat and colleagues investigated whether upregulation of epidermal growth factor receptor (EGFR) signalling—a pathway known to be insulin-responsive in other species—might explain the pathological changes seen in hyperinsulinaemic laminitis, examining lamellar tissue from healthy and affected horses and ponies using immunostaining, gene expression analysis, and phosphorylation studies, alongside measurements of circulating EGF concentrations. EGFR localisation to the secondary epidermal lamellae was confirmed, predominantly in parabasal rather than basal cells, but laminitis induction did not upregulate EGFR gene expression or produce significant phosphorylation, suggesting the receptor itself is not a primary driver of hyperinsulinaemic laminitis pathology. Notably, insulin-dysregulated ponies showed markedly elevated post-prandial plasma EGF concentrations—nearly three times higher than healthy controls (274 ± 90 versus 97.4 ± 20.9 pg/mL)—a finding not replicated in acutely insulin-infused horses, indicating a distinct metabolic phenotype in chronically dysregulated animals. Whilst EGFR signalling does not appear central to hyperinsulinaemic laminitis, the elevated circulating EGF in insulin-dysregulated ponies warrants further investigation and may represent an important biomarker or pathophysiological component in naturally occurring disease.
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Practical Takeaways
- •Elevated post-prandial EGF in insulin-dysregulated ponies suggests a potential biomarker worth monitoring, though its direct role in laminitis development requires further research
- •EGFR signalling upregulation is not the primary mechanism driving hyperinsulinemic laminitis, so therapeutic targeting of EGFR alone may not prevent or treat laminitis in these horses
- •Insulin dysregulation and post-feeding metabolic changes warrant closer investigation as alternative pathways in laminitis pathophysiology beyond the EGF system
Key Findings
- •EGFR localised to secondary epidermal lamellae with stronger staining in parabasal cells, but no change in EGFR gene expression occurred with laminitis induction
- •Post-prandial EGF concentrations in insulin-dysregulated ponies were nearly 3-fold higher than healthy ponies (274 ± 90 vs. 97.4 ± 20.9 pg/mL, P = 0.05)
- •EGFR showed some phosphorylation in laminitic tissue but does not appear to play a major pathogenic role in hyperinsulinemic laminitis