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Home / Equine Research Bank / PLoS One / Impact of laminitis on the canonical Wnt signaling pathway i...
PloS one2013; 8(2); e56025; doi: 10.1371/journal.pone.0056025

Impact of laminitis on the canonical Wnt signaling pathway in basal epithelial cells of the equine digital laminae.

Abstract: The digital laminae is a two layer tissue that attaches the distal phalanx to the inner hoof wall, thus suspending the horse's axial skeleton in the hoof capsule. This tissue fails at the epidermal:dermal junction in laminitic horses, causing crippling disease. Basal epithelial cells line the laminar epidermal:dermal junction, undergo physiological change in laminitic horses, and lose versican gene expression. Versican gene expression is purportedly under control of the canonical Wnt signaling pathway and is a trigger for mesenchymal-to-epithelial transition; thus, its repression in laminar epithelial cells of laminitic horses may be associated with suppression of the canonical Wnt signaling pathway and loss of the epithelial cell phenotype. In support of the former contention, we show, using laminae from healthy horses and horses with carbohydrate overload-induced laminitis, quantitative real-time polymerase chain reaction, Western blotting after sodium dodecylsulfate polyacrylamide gel electrophoresis, and immunofluorescent tissue staining, that positive and negative regulatory components of the canonical Wnt signaling pathway are expressed in laminar basal epithelial cells of healthy horses. Furthermore, expression of positive regulators is suppressed and negative regulators elevated in laminae of laminitic compared to healthy horses. We also show that versican gene expression in the epithelial cells correlates positively with that of β-catenin and T-cell Factor 4, consistent with regulation by the canonical Wnt signaling pathway. In addition, gene and protein expression of β-catenin correlates positively with that of integrin β4 and both are strongly suppressed in laminar basal epithelial cells of laminitic horses, which remain E-cadherin(+)/vimentin(-), excluding mesenchymal transition as contributing to loss of the adherens junction and hemidesmosome components. We propose that suppression of the canonical Wnt signaling pathway, and accompanying reduced expression of β catenin and integrin β4 in laminar basal epithelial cells reduces cell:cell and cell:basement membrane attachment, thus, destabilizing the laminar epidermal:dermal junction.
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Publication Date: 2013-02-06 PubMed ID: 23405249PubMed Central: PMC3566061DOI: 10.1371/journal.pone.0056025Google Scholar: Lookup
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  • Journal Article
  • Research Support
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  • Extramural
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  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research investigates the effects of laminitis, a debilitating disease that disrupts the connection between the horse’s hoof and the underlying bone, on the functionality of basal epithelial cells in the horse’s hoof. The study identifies a relationship between the disease and versican gene expression, controlled by the canonical Wnt signaling pathway, which is essential for cellular functions and structural changes.

Background of the Problem

  • The digital laminae, a two-layer tissue in a horse’s hoof connecting the distal phalanx (the bone in the toe of horse’s hoof) to the inner hoof wall, fails at the epidermal:dermal junction in horses suffering from laminitis. This results in a painful and often debilitating disease.
  • In laminitis, basal epithelial cells which are located on the junction experience physiological changes and lose the expression of the versican gene. This gene, controlled by the canonical Wnt signaling pathway, triggers a transition in the cells, known as the mesenchymal-to-epithelial transition.
  • Repression of the versican gene in laminitis could be associated with the suppression of the canonical Wnt signaling pathway, leading to a loss of the epithelial cell phenotype.

Methodology

  • Using a combination of a quantitative real-time polymerase chain reaction (a technique used to amplify and quantify a targeted DNA molecule), Western blotting (used to detect specific protein molecules in a sample), sodium dodecylsulfate polyacrylamide gel electrophoresis (a technique used to separate proteins by their electrophoretic mobility), and immunofluorescent tissue staining, the researchers demonstrated that positive and negative regulatory components of the canonical Wnt signaling pathway are expressed in healthy horse laminar basal epithelial cells.

Findings

  • The study found that positive regulators of the canonical Wnt signalling pathway are suppressed and negative regulators are elevated in laminitic horses compared to healthy horses. This implies that laminitis affects the regulation of the Wnt signalling pathway.
  • Further findings suggest that the expression of the versican gene in the epithelial cells correlates positively with that of β-catenin and T-cell Factor 4, showing a consistent regulation by the canonical Wnt signaling pathway. Also, the expression of β-catenin seems to have a positive correlation with integrin β4. Both are strongly suppressed in laminar basal epithelial cells of laminitic horses.

Conclusion

  • Researchers propose that the suppression of the canonical Wnt signaling pathway in laminitis, as well as the accompanying reduced expression of β-catenin and integrin β4 in laminar basal epithelial cells leads to a decrease in cell:cell and cell:basement membrane attachment.
  • This destabilizes the laminar epidermal:dermal junction, contributing to the progression and symptoms of laminitis.

Cite This Article

APA
Wang L, Pawlak EA, Johnson PJ, Belknap JK, Eades S, Stack S, Cousin H, Black SJ. (2013). Impact of laminitis on the canonical Wnt signaling pathway in basal epithelial cells of the equine digital laminae. PLoS One, 8(2), e56025. https://doi.org/10.1371/journal.pone.0056025

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 8
Issue: 2
Pages: e56025
PII: e56025

Researcher Affiliations

Wang, Le
  • Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, Massachusetts, United States of America.
Pawlak, Erica A
    Johnson, Philip J
      Belknap, James K
        Eades, Susan
          Stack, Sharon
            Cousin, Helene
              Black, Samuel J

                MeSH Terms

                • Animals
                • Blotting, Western
                • Cadherins / metabolism
                • Epithelial Cells / cytology
                • Epithelial Cells / metabolism
                • Fluorescent Antibody Technique
                • Horse Diseases / physiopathology
                • Horses
                • Inflammation
                • Integrin alpha6 / metabolism
                • Integrin beta4 / metabolism
                • Lameness, Animal / physiopathology
                • Signal Transduction
                • Vimentin / metabolism
                • Wnt Signaling Pathway
                • beta Catenin / metabolism

                Grant Funding

                • R01 DE016289 / NIDCR NIH HHS
                • DE016289 / NIDCR NIH HHS

                Conflict of Interest Statement

                The authors have declared that no competing interests exist.

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                Citations

                This article has been cited 6 times.
                1. Campolo A, Frantz MW, de Laat MA, Hartson SD, Furr MO, Lacombe VA. Differential Proteomic Expression of Equine Cardiac and Lamellar Tissue During Insulin-Induced Laminitis. Front Vet Sci 2020;7:308.
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