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 proliferating and migrating epithelial and connective tissue cells. This process includes the re-establishment of the continuous surface epithelial layer, glandular epithelial structures, microvessels and connective tissue within the
scar. Epithelial cells in the mucosa of the
ulcer margin proliferate and migrate onto the granulation tissue to re-epithelialize the
ulcer.
Growth 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-epithelialization and the reconstruction of glandular structures. These
growth factors, most notably
EGF, trigger epithelial cell proliferation via signal transduction pathways involving
EGF-R- MAP (Erk1/Erk2)
kinases. Granulation tissue, which develops at the
ulcer base, consists of fibroblasts, macrophages and proliferating endothelial cells, which form microvessels under the control of angiogenic
growth factors. These
growth factors [bFGF,
vascular endothelial growth factor (
VEGF) and
angiopoietins] promote angiogenesis--capillary vessel formation--thereby allowing for the reconstruction of microvasculature in the mucosal
scar, which is essential for delivery of
oxygen and nutrients to the healing site. The primary trigger to activate expression of angiogenic
growth factors and their receptors appears to be
hypoxia. During
ulcer healing expression of
growth factor genes is tightly regulated in a temporally and spatially ordered manner.