Epidermal growth factor explored in laminitis study

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Researchers have found that levels of epidermal growth factor (EGF) are elevated in insulin-dysregulated ponies after a meal, but they can’t explain why.

Average EGF concentrations in insulin dysregulated ponies after eating were almost three times higher than in healthy ponies, Melody A. de Laat and her colleagues reported in the open-access journal PLOS ONE.

In contrast, no difference was seen in EGF concentrations in horses.

The researchers set out in their study to learn more about how the EGF system works in cases of laminitis arising from high levels of insulin.

Laminitis affects the epidermal lamellae in the feet. Typically, there is epidermal cell proliferation and structural collapse.

High levels of insulin are a known driver, although the manner in which the disease develops is not completely understood.

Insulin is known to activate the EGF system in other species. This being the case, the researchers set out to determine whether that upregulation of EGF receptor signalling is a key factor in laminitis development in horses.

Receptors are proteins or glycoproteins that receive signals by binding to signaling molecules, that send a specific signal onward.

Activation of this particular receptor regulates cell proliferation, which is why it has been the focus of intense research in the field of cancer therapeutics.

Similar to cancer, equine laminitis is a disease that involves epidermal cell proliferation, in this case in the epidermal basal cells of the foot lamellae.

“If the EGF receptor could be implicated in laminitis pathophysiology an array of new therapeutic options for treating the disease could be readily adapted from cancer therapeutics for laminitis treatment,” the authors said.

For their study, they examined hoof tissue from healthy Standardbred horses and those with induced hyperinsulinemia and laminitis for EGF receptor distribution and quantity using immunostaining and gene expression, respectively.

Next, plasma EGF concentrations were compared in healthy and insulin-infused horses, and in healthy and insulin-dysregulated ponies before and after feeding.

The researchers found that no change in EGF receptor gene expression occurred with laminitis, although the receptor showed some phosphorylation — the most common mechanism of regulating protein function and transmitting signals throughout the cell.

The study team said their findings indicated that the EGF receptor is unlikely to be a disease-causing factor in insulin-associated laminitis. “But that it might play a role, at least in part, in epidermal repair.”

It is unknown whether their findings are also applicable to other forms of laminitis, such as the inflammatory and septic variants, they said.

Based on the data, they surmise that laminitis is a multifactorial event, with the involvement of many pathways and factors.

“As a result, we have farther to go with respect to understanding this disease.”

The evidence, they said, pointed a potentially synergistic relationship between insulin and EGF.

“Our understanding of equine insulin dysregulation in limited, but the disease is common and is a significant risk factor for laminitis.

“The finding that EGF is increased in insulin-dysregulated ponies has identified a direction for future research into metabolic dysfunction.”

It deserves further investigation, they said.

The study team comprised de Laat, Robert Spence and Martin Sillence, all from the Queensland University of Technology; and Christopher Pollitt, from the University of Queensland.

de Laat MA, Spence RJ, Sillence MN, Pollitt CC (2019) An investigation of the equine epidermal growth factor system during hyperinsulinemic laminitis. PLoS ONE 14(12): e0225843. https://doi.org/10.1371/journal.pone.0225843

The study, published under a Creative Commons License, can be read here

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