Equine laminitis: glucose deprivation and MMP activation induce dermo-epidermal separation in vitro.

This study investigates how glucose deprivation and metalloproteinase (MMP) activation in horse hoof (equine) lamellar explants cause a separation between the dermal and epidermal layers, leading to a condition known as laminitis. It suggests that therapies to improve peripheral glucose uptake and suppress MMP activation could help prevent or manage this disease.

Research Methodology

• The researchers cultured hoof lamellar explants in a controlled environment with either no glucose or exposed to an MMP activator known as p-amino-phenol-mercuric acetate (APMA).
• These explants were then subjected to tension, simulating the physical stress these tissues might experience in a living organism, and processed for observation under transmission electron microscopy (TEM).

Findings

• Under tension, explants deprived of glucose, as well as those exposed to APMA, separated at the junction between the dermal and epidermal layers.
• The separation happened through two different microscopic processes. In glucose-starved samples, the number of tiny protein anchors known as hemidesmosomes (HDs) within the cells decreased until they disappeared entirely, leading to the collapse of the cell’s internal structure.
• The anchoring filaments (AFs), proteins that connect the cell to the basement membrane, were not affected in glucose-deprived samples. However, they failed under tension, contributing to the dermo-epidermal separation.
• Conversely, in the presence of the MMP activator APMA, the HDs were not affected, but the AFs disappeared, leading again to a dermo-epidermal separation.

Conclusions

• The results suggest that the condition of laminitis might occur in situations where glucose uptake is compromised, as in cases of equine Cushing’s disease, obesity, hyperlipaemia, ischaemia and septicaemia. It could also occur owing to overactivation of MMPs, such as in cases of carbohydrate overload.
• Based on these findings, the authors suggest that treatments focused on facilitating peripheral glucose uptake and controlling MMP activation may be effective strategies to prevent or manage laminitis in horses.