Regeneration of gastric mucosa during ulcer healing is triggered by growthfactors and signal transduction pathways

An ulcer is a deep necrotic lesion penetrating through the entire thickness of the gastrointestinal mucosa and muscularis mucosae. Ulcer healing is a complex and tightly regulated process of filling the mucosal defect with pr oliferating and migrating epithelial and connective tissue cells. This proc ess includes the re-establishment of the continuous surface epithelial laye r, glandular epithelial structures, microvessels and connective tissue with in the scar. Epithelial cells in the mucosa of the ulcer margin proliferate and migrate onto the granulation tissue to re-epithelialize the ulcer. Gro wth factors, such as epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), trefoil peptides (TP), platelet derived growth factor (PDGF ) and other cytokines produced locally by regenerating cells, control re-ep ithelialization and the reconstruction of glandular structures. These growt h factors, most notably EGF, trigger epithelial cell proliferation via sign al transduction pathways involving EGF-R- MAP (Erk1/Erk2) kinases. Granulat ion tissue, which develops at the ulcer base, consists of fibroblasts, macr ophages and proliferating endothelial cells, which form microvessels under the control of angiogenic growth factors. These growth factors [bFGF, vascu lar endothelial growth factor (VEGF) and angiopoietins] promote angiogenesi s-capillary vessel formation-thereby allowing for the reconstruction of mic rovasculature in the mucosal scar, which is essential for delivery of oxyge n and nutrients to the healing site. The primary trigger to activate expres sion of angiogenic growth factors and their receptors appears to be hypoxia . During ulcer healing expression of growth factor genes is tightly regulat ed in a temporally and spatially ordered manner. (C) 2001 Published by Else vier Science Ltd.