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PloS one2019; 14(12); e0225843; doi: 10.1371/journal.pone.0225843

An investigation of the equine epidermal growth factor system during hyperinsulinemic laminitis.

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.
Publication Date: 2019-12-05 PubMed ID: 31805097PubMed Central: PMC6894753DOI: 10.1371/journal.pone.0225843Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research explores the relationship between the epidermal growth factor system and equine laminitis, a disease usually caused by hyperinsulinemia. The study specifically tests whether an increase in epidermal growth factor receptor signalling plays a part in developing the disease, with the results suggesting further investigation is needed.

Introduction

  • The research focuses on equine laminitis, a disease that affects the hooves of horses, specifically the digital epidermal lamellae structure. This disease is mostly brought about by an excessive amount of insulin (hyperinsulinemia).
  • The association between the disease and hyperinsulinemia is not well-understood. Insulin has been observed to influence the epidermal growth factor (EGF) system in other species. The EGF system involves the epidermal growth factor receptor (EGFR), which the researchers believe can play a critical role in the progression of laminitis.

Methodology

  • Researchers first observed lamellar tissue taken from healthy Standardbred horses. Similar observations were made on horses, which were artificially induced with hyperinsulinemia and laminitis.
  • The researchers utilized immunostaining and gene expression methods to determine the EGFR distribution and quantity. They also quantified the level of phosphorylation of the EGFR.
  • They further analyzed plasma EGF concentrations and compared the levels before and after feeding in healthy horses, insulin-infused horses, and insulin-dysregulated ponies.

Results

  • The observations found EGFR localized in the secondary epidermal lamellae with more potent stains in parabasal cells compared to basal cells.
  • No significant change was seen in the gene expression of EGFR in relation to laminitis. However, some phosphorylation of the receptor was observed.
  • No difference was observed regarding EGF concentrations in horses. However, in insulin-dysregulated ponies, mean post-feeding EGF concentrations were seen to nearly triple compared to those in healthy ponies.

Conclusion

  • The study concludes that EGFR does not seem to significantly contribute to the pathological progression of hyperinsulinemic laminitis.
  • However, the observable increase of EGF in insulin-dysregulated ponies indicates a possible association or role in the disease pathophysiology, suggesting further studies to deepen our understanding of this connection.

Cite This Article

APA
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

Publication

ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 14
Issue: 12
Pages: e0225843
PII: e0225843

Researcher Affiliations

de Laat, Melody A
  • Earth, Environmental and Biological Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.
Spence, Robert J
  • Earth, Environmental and Biological Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.
Sillence, Martin N
  • Earth, Environmental and Biological Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.
Pollitt, Christopher C
  • School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia.

MeSH Terms

  • Animals
  • Epidermal Growth Factor / blood
  • Epidermal Growth Factor / metabolism
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Foot Diseases / blood
  • Foot Diseases / veterinary
  • Gene Dosage
  • Gene Expression Regulation
  • Hoof and Claw / pathology
  • Horse Diseases / blood
  • Horse Diseases / metabolism
  • Horses / blood
  • Hyperinsulinism / blood
  • Hyperinsulinism / complications
  • Insulin / metabolism
  • Phosphorylation

Conflict of Interest Statement

The authors have declared that no competing interests exist.

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