LOCALIZATION OF EPIDERMAL GROWTH-FACTOR TRANSFORMING GROWTH-FACTOR-ALPHA RECEPTOR IN THE HUMAN GASTRIC-MUCOSA - AN IMMUNOHISTOCHEMICAL AND IN-SITU HYBRIDIZATION STUDY

Current evidence indicates that epidermal growth factor (EGF) and tran sforming growth factor-alpha (TGF-alpha) play a pivotal role in the ma intenance of gastric mucosal integrity, via binding to a common cell-s urface receptor (EGF/TGF-alpha receptor). We examined the distribution and cellular sites of synthesis of EGF/TGF-alpha receptor in normal h uman gastric mucosa by immunohistochemical and in situ hybridization t echniques. Intense EGF/TGF-alpha receptor immunoreactivity was observe d in the basal cytoplasm and along basolateral membranes of mucus neck cells, foveolar columnar cells, and surface epithelial cells facing t he gastric lumen. Parietal cells and mucus-secreting pyloric gland cel ls displayed a distinct basolateral immunostaining, whereas the lumina l membrane was unstained. Immunoreactivity was also noted in spindle-s haped cells of the lamina propria and in smooth muscle cells of the mu scularis mucosae and muscularis propria. In situ hybridization reveale d EGF/TGF-alpha receptor RNA transcripts in all cell types displaying positive immunoreaction. These results suggest a physiological role fo r EFG/TGF-alpha in the regulation of multiple gastric functions. The r eceptor distribution at the luminal aspect of the gastric mucosa provi des the anatomical basis for a possible interaction of gastric juice E GF (or TGF-alpha) with cells of the mucosal surface, whereas the expre ssion of EGF/TFG-alpha receptor in cells which are not in direct conta ct with the gastric lumen is consistent with blood-mediated or paracri ne/autocrine mechanisms of EGF/TGF-alpha action on these cells.