Impact of laminitis on the canonical Wnt signaling pathway in basal epithelial cells of the equine digital laminae.
Authors: Wang Le, Pawlak Erica A, Johnson Philip J, Belknap James K, Eades Susan, Stack Sharon, Cousin Helene, Black Samuel J
Journal: PloS one
Summary
# Editorial Summary The digital laminae's failure at the epidermal–dermal junction is the pathological hallmark of laminitis, yet the cellular mechanisms driving this catastrophic loss of attachment remain incompletely understood. Wang and colleagues investigated whether suppression of the canonical Wnt signalling pathway in basal epithelial cells might explain the progressive weakening of laminar structure, using quantitative PCR, Western blotting, and immunofluorescent staining to compare healthy laminae with tissue from horses with carbohydrate overload-induced laminitis. In laminitic horses, positive regulators of Wnt signalling were significantly downregulated whilst negative regulators were elevated; crucially, β-catenin and integrin β4—both essential for cell–cell and cell–basement membrane adhesion—showed marked suppression in basal epithelial cells, yet cells retained their epithelial phenotype without transitioning to mesenchymal characteristics. These findings suggest that laminitis involves a selective, Wnt-pathway-mediated loss of adhesion molecules rather than a fundamental change in cell identity, pointing towards potential intervention points targeting this signalling cascade before structural failure occurs. For practitioners, this work highlights that laminitis involves specific molecular derangements upstream of visible tissue damage, opening discussion around whether early detection of Wnt pathway suppression or adhesion molecule loss might become clinically useful markers for intervention.
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Practical Takeaways
- •Understanding that laminitis involves suppression of specific signaling pathways at the cellular level may inform development of targeted therapies to stabilize the laminar attachment in acute cases
- •The mechanism identified (loss of adhesion molecules rather than cell phenotype change) suggests therapeutic interventions should focus on restoring epithelial attachment rather than preventing cell differentiation
- •This research identifies potential molecular targets (Wnt pathway components, β-catenin, integrin β4) that could be modulated to preserve or restore laminar integrity in laminitis management
Key Findings
- •Positive regulators of canonical Wnt signaling pathway are suppressed in laminitic laminae while negative regulators are elevated compared to healthy tissue
- •β-catenin and integrin β4 expression are strongly reduced in laminar basal epithelial cells of laminitic horses, correlating with versican gene expression loss
- •Suppression of Wnt signaling reduces cell-cell and cell-basement membrane attachment without triggering mesenchymal transition, destabilizing the laminar epidermal-dermal junction