Mechanism of gastric mucosal proliferation induced by gastrin

Gastrin has a potent trophic effect on gastric fundic mucosa. When serum co ncentrations of gastrin are elevated, proliferation of both the progenitor cells in the glandular neck zone and enterochromaffin-like (ECL) cells in t he bottom of the glands is stimulated. Because ECL cells have gastrin recep tors, their proliferation is directly stimulated by gastrin. However, becau se the proliferation of progenitor cells cannot be directly stimulated (so far there has been no gastrin receptor demonstrated on these proliferating cells), some indirect mechanisms must be involved. Enterochromaffin-like an d parietal cells are only two types of cells that have demonstrated a stron g gene expression of the gastrin receptor. Furthermore, they secrete severa l growth factors, such as Reg protein, heparin-binding epidermal growth fac tor-like growth factor (HB-EGF) and amphiregulin (AR). Reg protein producti on by ECL cells, as well as HB-EGF and AR production by parietal cells, is stimulated by gastrin and these growth factors are potent trophic agents of progenitor cells in the neck zone of the gastric fundic mucosa. Accordingl y, gastrin may stimulate the proliferation of gastric mucosal cells indirec tly via these growth factors in addition to its direct trophic effect on EC L cells. (C) 2000 Blackwell Science Asia Pty Ltd.