title: Gene expression in the lamellar dermis-epidermis during the developmental phase of carbohydrate overload-induced laminitis in the horse.
abstract: OBJECTIVE
  Gene expression in the lamellar dermis and epidermis was compared between healthy horses and horses in the developmental phase of carbohydrate overload-induced laminitis, in order to better understand the local biochemical and cellular events involved in the pathogenesis of laminitis.
  
  
  METHODS
  Six healthy adult horses, with no history or clinical evidence of laminitis.
  
  
  METHODS
  Horses were randomly divided into two groups: control (n=3) and laminitis (n=3). Control horses received no treatment and were humanely euthanatized at the same time as the laminitis group. Horses in the laminitis group were given oligofructose (10g/kg bwt by nasogastric tube) and humanely euthanatized 24-30h later, before any clinical signs of laminitis were apparent. Sections of lamellar dermis and epidermis were harvested from the dorsal hoof wall of each horse immediately after death and cryopreserved until analysis. A bovine microarray chip, comprising approximately 15,000 genes, was used to compare gene expression between laminitis and control groups.
  
  
  RESULTS
  A total of 155 genes were up-regulated in the laminitis group. No genes were down-regulated. Genes coding for the production of pro-inflammatory biochemical or cellular processes and those involved in protein degradation/turnover predominated. Several regulatory or anti-inflammatory genes were also up-regulated.
  
  
  CONCLUSIONS
  Generation of inflammatory mediators within the lamellar tissues occurred before the development of substantial dermal-epidermal separation, inflammatory infiltrate, or vascular changes, and before the horses began showing signs of foot pain. While further studies are needed, early and targeted anti-inflammatory therapy may halt or prevent the development of laminitis in at-risk individuals.
authors.affiliation: Department of Surgery, School of Medicine, University of Pennsylvania, Pennsylvania, United States.
authors.forename: Murat T
authors.initials: MT
authors.lastname: Budak
authors.forename: James A
authors.initials: JA
authors.lastname: Orsini
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Pollitt
authors.forename: Neal A
authors.initials: NA
authors.lastname: Rubinstein
mesh_terms: D051722:ADAM Proteins / Q000235:genetics; D000071121:ADAMTS4 Protein; D000818:Animals; D020405:Dermis / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D004817:Epidermis / Q000378:metabolism; D005534:Foot Diseases / Q000378:metabolism / Q000662:veterinary*; D020869:Gene Expression Profiling; D006724:Hoof and Claw / Q000378:metabolism*; D006734:Horse Diseases / Q000378:metabolism*; D006736:Horses; D008070:Lipopolysaccharides / Q000494:pharmacology; D011348:Procollagen N-Endopeptidase / Q000235:genetics
chemical_list: D004040:Dietary Carbohydrates; D008070:Lipopolysaccharides; D051722:ADAM Proteins; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein