Localization of epidermal growth factor/transforming growth factor-α receptor in the human gastric mucosa

Abstract

Current evidence indicates that epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) play a pivotal role in the maintenance of gastric mucosal integrity, via binding to a common cell-surface receptor (EGF/TGF-alpha receptor). We examined the distribution and cellular sites of synthesis of EGF/TGF-alpha receptor in normal human gastric mucosa by immunohistochemical and in situ hybridization techniques. Intense EGF/TGF-alpha receptor immunoreactivity was observed in the basal cytoplasm and along basolateral membranes of mucus neck cells, foveolar columnar cells, and surface epithelial cells facing the gastric lumen. Parietal cells and mucus-secreting pyloric gland cells displayed a distinct basolateral immunostaining, whereas the luminal membrane was unstained. Immunoreactivity was also noted in spindle-shaped cells of the lamina propria and in smooth muscle cells of the muscularis mucosae and muscularis propria. In situ hybridization revealed EGF/TGF-alpha receptor RNA transcripts in all cell types displaying positive immunoreaction. These results suggest a physiological role for EGF/TGF-alpha in the regulation of multiple gastric functions. The receptor distribution at the luminal aspect of the gastric mucosa provides the anatomical basis for a possible interaction of gastric juice EGF (or TGF-alpha) with cells of the mucosal surface, whereas the expression of EGF/TGF-alpha receptor in cells which are not in direct contact with the gastric lumen is consistent with blood-mediated or paracrine/autocrine mechanisms of EGF/TGF-alpha action on these cells.

Role of growth factors and their receptors in gastric ulcer healing

“…In this tissue, the EGF-R is prevalently distributed along the basolateral membrane of surface and glandular cells while it is scarcely present on the luminal membrane (Orsini et al, 1993;Playford et al, 1996;Tarnawski et al, 1991) ( Fig. 3A and B).…”

Subcellular distribution of peptides associated with gastric mucosal healing and neoplasia

“…When extracted from human urine, EGF/URO inhibits human gastric acid secretion and is effective in the stimulation of cell proliferation in response to injury; this has important implications in healing of damaged gastric mucosa and in the rat EGF accelerates ulcer healing due to its mitogenic activity (Konturek et al, 1988). Both TGF a and EGF also play central roles in the maintenance of the integrity of the healthy gastric mucosa (Orsini et al, 1993), but EGF production is restricted to mucous neck cells, while extensive local production of TGF a protein and mRNA (Beauchamp et al, 1989) indicate perhaps that TGF a exercises more influence in this organ; Lee et al (1991) found little EGF immunoreactivity in the normal rat oxyntic mucosa, while TGF a immunoreactivity is widespread .…”

“…9) at the plasma membrane, so that in some cases antigenicity at a certain location on the plasma membrane is so intense that individual gold grains can scarcely be perceived; this clustering, optimises the efficiency of the receptor for lateral prox- imation and thus autophosphorylation of the dimer (Van Belzen et al, 1988). Mucous neck cells exhibit the same localization while EGFR immunoreactivity in parietal cells and mucus-secreting pyloric gland cells is even more specifically associated with the basolateral cell membranes (Orsini et al, 1993); thus the activation of the receptor is suggested to have a direct effect on hydrochloric acid production in the stomach (Mori et al, 1987). In normal rat stomach EGFR immunoreactivity is found in proliferative zone cells and some pa-rietal cells (Tarnawski et al, 19921, and in mucous neck cells (Lee et al, 1991).…”

The role of growth factors in intestinal regeneration and repair in necrotizing enterocolitis

“…22 The EGF receptor (EGFR) has tyrosine kinase activity and is localized primarily on the basolateral surface of the enterocytes, however, apical EGFR activity has been observed. 23-30 Recent work from our laboratory has shown that the proliferative effects of EGF are preserved despite loss of the enterocyte EGFR, suggesting that EGFR activity in the underlying submucosa and muscularis layers of the bowel may also play a role. 31 The importance of EGF in gut development is highlighted by the fact that global EGFR deletion is associated with embryonic lethality.…”