Abstract
Equine laminitis is a disease of the digital epidermal lamellae typified by epidermal cell proliferation and structural collapse. Most commonly the disease is caused by hyperinsulinemia, although the pathogenesis is incompletely understood. Insulin can activate the epidermal growth factor (EGF) system in other species and the present study tested the hypothesis that upregulation of EGF receptor (EGFR) signalling is a key factor in laminitis pathophysiology. First, we examined lamellar tissue from healthy Standardbred horses and those with induced hyperinsulinemia and laminitis for EGFR distribution and quantity using immunostaining and gene expression, respectively. Phosphorylation of EGFR was also quantified. Next, plasma EGF concentrations were compared in healthy and insulin-infused horses, and in healthy and insulin-dysregulated ponies before and after feeding. The EGFR were localised to the secondary epidermal lamellae, with stronger staining in parabasal, rather than basal, cells. No change in EGFR gene expression occurred with laminitis, although the receptor showed some phosphorylation. No difference was seen in EGF concentrations in horses, but in insulin-dysregulated ponies mean, post-prandial EGF concentrations were almost three times higher than in healthy ponies (274 ± 90 vs. 97.4 ± 20.9 pg/mL, P = 0.05). Although the EGFR does not appear to play a major pathogenic role in hyperinsulinemic laminitis, the significance of increased EGF in insulin-dysregulated ponies deserves further investigation.
Highlights
Despite steady progress, and improved clarity around the disease’s causative factors, research into equine laminitis has not yet determined the exact pathophysiological mechanism of this common disease
There was abundant positive staining for the epidermal growth factor receptor (EGFR) throughout the lamellae both in the control horses, where lamellae had the typical appearance of a healthy dermo-epidermal interface, and of horses in the developmental and acute stages of insulin-induced laminitis
The EGFR is a tyrosine-kinase receptor that is integral in epithelial cell biology
Summary
Improved clarity around the disease’s causative factors, research into equine laminitis has not yet determined the exact pathophysiological mechanism of this common disease. Laminitis is a painful and costly disease for the equine population worldwide [1]. The outcome of severe laminitis, the distraction of the pedal bone away from the hoof wall, is straightforward to diagnose and understand. The determinants of this detachment have proven to be far more difficult to identify [1].
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