title: Distribution of epidermal growth factor receptor (EGFr) in normal and acute peptic-injured equine gastric squamous epithelium.
abstract: Growth factors are important in healing and restoration of injured gastrointestinal tissues and, therefore, we characterised temporally the distribution and density of epidermal growth factor receptor (EGFr) in normal and peptic-injured gastric squamous epithelium of horses. Lesions were induced in the equine gastric squamous epithelium using a feed deprivation protocol that results in prolonged increased gastric acidity. Fifteen mature horses, 9 geldings and 6 mares, age 3 to 20 years, were used and divided into 3 groups: Group 1 (n = 5) were subjected to euthanasia for problems unrelated to the gastrointestinal tract and had normal-appearing gastric squamous mucosal epithelium; Groups 2 (n = 5) and 3 (n = 5) had lesions induced in the gastric squamous epithelium by alternating 24 h periods of feed deprivation and ad libitum access to hay, for a total of 48 h and 96 h, respectively. Following lethal injection of a barbiturate, stomachs were removed and fixed by filling with 4- 6 l 10% buffered formalin. Sections were made from normal stomachs and lesions in the gastric squamous epithelium adjacent to the margo plicatus along the right side of the stomach/greater curvature and the lesser curvature. A modified avidin-biotin immunoperoxidase technique was used to stain the formalin-fixed tissue specimens for EGFr. A computerised image analysis system was used to measure area occupied by EGFr (EGFr area) and mean EGFr density in 4 zones within the epithelium extending from the basal cell layers toward the lumen. Measurements were made of epithelium in an erosion bed, at the margin of an ulcer or erosion, and 10-15 mm distant from the lesion margin. Additionally, EGFr area and density were measured in epithelial cells adjacent to capillaries in the epithelium. Intermittent feed deprivation resulted in erosion and ulceration of the gastric squamous epithelium of each horse. Mean EGFr area and density were greatest (P<0.05) in the basal layer of epithelia from all horses, and EGFr staining diminished progressively toward the lumen. Tissues from Group 3 had significantly greater EGFr area in the lesion margin than epithelia from Group 2. EGFr density was less in the epithelia of erosion beds from Groups 2 and 3 compared to normal epithelium, and EGFr area in Group 2 erosion bed epithelia was significantly less than in normal epithelium and epithelia of Group 3. EGFr area in cells adjacent to epithelial capillaries of Group 3 was significantly greater than that of Group 1. Mitotic cell activity was significantly greater in epithelia associated with ulcers and erosions in Groups 2 and 3 compared to normal tissues from Group 1 horses. Staining for EGFr in the glandular mucosa adjacent to squamous epithelium at the margo plicatus was inconsistent and typically faint when present. EGFr distribution in equine gastric squamous epithelium was greatest in regions of greatest cell proliferation, and these areas were in the basal layers of epithelium and immediately adjacent to capillaries. There was evidence that EGFr is induced in peptic-injured equine gastric squamous epithelium. A receptor ligand, EGF or transforming growth factoralpha, may be a factor in healing of gastric squamous mucosal ulcers in horses. Further research should be directed at identifying this ligand and determining its origin in equine gastric mucosa.
authors.affiliation: Marion duPont Scott Equine Medical Center, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Leesburg 20177, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Jeffrey
authors.forename: M J
authors.initials: MJ
authors.lastname: Murray
authors.forename: E S
authors.initials: ES
authors.lastname: Eichorn
mesh_terms: D000818:Animals; D002455:Cell Division; D004848:Epithelium / Q000378:metabolism; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000302:isolation & purification; D005260:Female; D005508:Food Deprivation; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D006734:Horse Diseases / Q000378:metabolism* / Q000473:pathology; D006736:Horses; D007124:Immunoenzyme Techniques / Q000662:veterinary; D008297:Male; D013276:Stomach Ulcer / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*
chemical_list: D066246:ErbB Receptors