Role of Platelets in Gastric Ulcer Healing: A Delivery System for Growth Factors

Abstract

Gastric ulcers are deep, necrotic lesions that involve the full thickness of the mucosa and penetrate through the muscularis mucosae. Ulcer healing is an active and complicated process of filling the mucosal defect with proliferating and migrating epithelial cells and connective components, so as to reconstruct the mucosal architecture. This requires the concerted interaction of a variety of tissues and cellular systems, including soluble mediators, formed blood elements, extracellular matrix (ECM) and parenchymal cells. Tissue damage leads to blood vessel disruption accompanied by extravasation of blood constituents. Tissue repair is initiated with the aggregation of platelets, formation of a fibrin clot, and the release of growth factors from the activated coagulation pathways, injured cells, platelets and ECM, followed by migration of inflammatory cells to the wound site. Thereafter, epithelial cells migrate over the damage, angiogenesis is initiated, and fibroblasts deposit and remodel the granulation tissue. Those processes are regulated by a complex network of highly divergent factors, among them a broad spectrum of structurally distinct regulatory peptides that have been identified within the gastric mucosa and platelets. Epidermal growth factor (EGF), hepatocyte growth factor (HGF), transforming growth factor (TGF)-, and insulin-like growth factor (IGF) are mainly involved in the reconstitution of epithelial structure. Platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), vascular endothelial cell growth factor (VEGF) and TGF- play major roles in the reconstitution of connective tissue, including vessels and smooth muscle cells, and the formation of ECM substrate for cell migration and differentiation. The expression of these growth factors and their receptors is increased during ulcer healing. Inhibition of their effects by neutralization with antibodies may