Gastrin-dependent expansion of Cck2r + corpus progenitors accelerates ulcer healing and inhibits gastric dysplasia

BACKGROUND: The cholecystokinin-2/gastrin receptor (Cck2r) is expressed in corpus isthmus progenitor, enterochromaffin-like and parietal cells, regulating acid secretion and cell turnover. However, the role of gastrin on Cck2r progenitors during mucosal regeneration remains unexplored. OBJECTIVE: To study the role of gastrin-Cck2r axis and corpus progenitors during gastric injury and regeneration. DESIGN: gastritis and N-Nitroso-N-Methylurea (MNU) exposure. RESULTS: 0.05), while hypergastrinaemia was protective. Similarly, in the MNU model, G-cell ablation worsened gastric pathology while hypergastrinaemia mitigated it. CONCLUSIONS: We report a novel role for G-cell-derived gastrin in ulcer healing. Hypogastrinaemia is a risk factor for poor ulcer healing, corpus atrophy and potentially cancer, while physiological gastrin responses are protective. PPI-induced hypergastrinaemia plays a key role in ulcer healing, and gastrin signalling may prevent gastric preneoplasia.