IN-VITRO WOUND REPAIR BY HUMAN GASTRIC FIBROBLASTS - IMPLICATIONS FORULCER HEALING

Fibroblasts modulate epithelial biological activities and play a key r ole in the ulcer healing process. There is no information regarding th e biological response of human gastric fibroblasts to regulatory compo unds. The aim of this study was to assess the effects of growth factor s and prostaglandins on an in vitro model of human gastric fibroblast wound repair. Subconfluent fibroblast cultures were used to study prol iferative responses, determined by [H-3]thymidine incorporation into D NA. In vitro wound repair was determined in confluent fibroblast monol ayers after mechanical denudation, The presence of putative growth fac tors secreted by fibroblasts was studied in conditioned medium by hepa rin-affinity chromatography and immunodetection with specific antibodi es. Serum and platelet-derived growth factor (PDGF)-BB induced a drama tic increase in both gastric fibroblast proliferation and closure of w ounded cell monolayers: whereas these activities were inhibited by bot h transforming growth factor (TGF)-beta(1) and prostaglandin E-1. Basa l activities in unstimulated gastric fibroblasts were lower than those obtained in skin fibroblasts, Conditioned medium stimulated fibroblas t proliferation and wound repair activity, which was inhibited by the addition of suramin, and was partially dependent on the presence of PD GF-like factor. PDGF is a major, autocrine promotor of human gastric f ibroblast-dependent wound repair activities, which are inhibited by pr ostaglandins and TGF-beta. These findings might be important for futur e therapeutic ulcer healing approaches.