Equine laminitis: glucose deprivation and MMP activation induce dermo-epidermal separation in vitro.
BACKGROUND
Acute laminitis is characterised by hoof lamellar dermal-epidermal separation at the basement membrane (BM) zone. Hoof lamellar explants cultured in vitro can also be made to separate at the basement membrane zone and investigating how this occurs may give insight into the poorly understood pathophysiology of laminitis.


OBJECTIVE
To investigate why glucose deprivation and metalloproteinase (MMP) activation in cultured lamellar explants leads to dermo-epidermal separation.


METHODS
Explants, cultured without glucose or with the MMP activator p-amino-phenol-mercuric acetate (APMA), were subjected to tension and processed for transmission electron microscopy (TEM).


RESULTS
Without glucose, or with APMA, explants under tension separated at the dermo-epidermal junction. This in vitro separation occurred via 2 different ultrastructural processes. Lack of glucose reduced hemidesmosomes (HDs) numbers until they disappeared and the basal cell cytoskeleton collapsed. Anchoring filaments (AFs), connecting the basal cell plasmalemma to the BM, were unaffected although they failed under tension. APMA activation of constituent lamellar MMPs did not affect HDs but caused AFs to disappear, also leading to dermo-epidermal separation under tension.


CONCLUSIONS
Natural laminitis may occur in situations where glucose uptake by lamellar basal cells is compromised (e.g. equine Cushing's disease, obesity, hyperlipaemia, ischaemia and septicaemia) or when lamellar MMPs are activated (alimentary carbohydrate overload).


CONCLUSIONS
Therapies designed to facilitate peripheral glucose uptake and inhibit lamellar MMP activation may prevent or ameliorate laminitis.
French
K R
KR
Australian Equine Laminitis Research Unit, School of Veterinary Science, Faculty of Natural Resources Agriculture and Veterinary Science, The University of Queensland, Brisbane 4072, Australia.
Pollitt
C C
CC
D000208:Acute Disease; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D046508:Culture Techniques / Q000662:veterinary; D004789:Enzyme Activation; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D005534:Foot Diseases / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D005947:Glucose / Q000008:administration & dosage* / Q000378:metabolism; D006724:Hoof and Claw / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D006734:Horse Diseases / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D006736:Horses; D007249:Inflammation / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000662:veterinary; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission / Q000662:veterinary; D010662:Phenylmercuric Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology
C010024:4-aminophenylmercuriacetate; D020782:Matrix Metalloproteinases; D005947:Glucose; D010662:Phenylmercuric Acetate