Cellular mechanisms, interactions, and dynamics of gastric ulcer healing

Abstract

An ulcer is a deep, focal defect in the gastric or duodenal wall penetrating through the entire thickness of mucosa and muscularis mucosae. Ulcer healing (i.e., the reconstruction of the muscularis mucosae and mucosal architecture) is an active process of filling the mucosal defect with proliferating and migrating epithelial cells and connective tissue. Mucosa adjacent to the ulcer creater forms a healing zone. Gastric glands in this zone dilate and the epithelial cells lining these glands dedifferentiate, express epidermal growth factor (EGF) receptor, and proliferate. The proliferation is triggered by local activation of genes encoding for EGF and its receptor. From the ulcer margin, proliferating epithelial cells migrate onto the granulation tissue to cover (re-epithelialize) the ulcer and bud into granulation tissue to reconstruct gastric glands in the ulcer scar. Re-epithelialization and reconstruction of epithelial structures are under control of EGF and related peptides produced locally by regenerating cells. Granulation tissue at the ulcer base (whose growth is regulated, at least in part, by fibroblast growth factors) supplies microvessels for restoration of the microvascular network and connective tissue for restoration of the lamina propria within the mucosal scar. The ulcer healing reflects a dynamic interaction between the epithelial component from the healing zone at the ulcer margin and the connective tissue component (including microvessels) originating from the granulation tissue.