Distribution of epidermal growth factor receptor (EGFr) in normal and acute peptic‐injured equine gastric squamous epithelium
Authors: JEFFREY S. C. , MURRAY M. J. , EICHORN E. S. 
Published: April 2007

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) and3(n = 5) had lesions induced in the gastric squamous epithelium by alternating 24 h periods of feed deprivation andad libitumaccess 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 themargo plicatusalong the right side of the stomach/greatercurvature and the lesser curvature. A modified avidin‐biotin immunoperoxidase technique was used to stain the formalinfixed 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 fromGroup 3had significantly greater EGFr area in the lesion margin than epithelia fromGroup 2.EGFr density was less in the epithelia of erosion beds fromGroups 2and3compared to normal epithelium, and EGFr area inGroup 2erosion bed epithelia was significantly less than in normal epithelium and epithelia ofGroup 3.EGFr area in cells adjacent to epithelial capillaries ofGroup 3was significantly greater than that ofGroup 1.Mitotic cell activity was significantly greater in epithelia associated with ulcers and erosions inGroups 2and3compared to normal tissues fromGroup 1horses. Staining for EGFr in the glandular mucosa adjacent to squamous epithelium at themargo plicatuswas 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 factorα, 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.