Growth factors in ulcer healing: Lessons from recent studies

Growth factors such as epidermal growth factor (EGF), basic fibroblast grow th factor (bFGF), platelet-derived growth factor (PDGF) and more recently v ascular endothelial growth factor (VEGF) have been used extensively to heal experimental gastric, duodenal and colonic ulcers in animal models. Encour aging results have been reported in clinical trials with EGF and bFGE. Sinc e our laboratory has been involved with the initial nicer healing studies w ith bFGF, PDGF and VEGF, we summarize here the major lessons from these stu dies and from literature data. These conclusions relate to the role of: 1) gastrointestinal (GI) secretion; 2) epithelial versus vascular components o f the healing; 3) efficacy in the upper and lower GI tract; 4) quality of u lcer healing; as well as 5) the endogenous origin; and 6) molar potency of growth factors. Namely, among these growth factors only EGF inhibits gastri c acid and stimulates duodenal bicarbonate secretion, while chronic adminis tration of bFGF slightly enhances gastric secretion and PDGF has no effect demonstrating that potent ulcer healing can be achieved without influencing acid base and mucus secretion. This might be related to the fact that thes e growth factors stimulate with varying potency virtually all the cellular elements needed for ulcer healing, e.g., epithelial cell proliferation and migration by EGF > bFGF > PDGF, fibroblast proliferation by bFGF > PDGF and angiogenesis by VEGF > bFGF much greater than PDGF much greater than EGF. Conceptually, the most interesting results were obtained recently with VEGF which is virtually specific for angiogenesis, illustrating that stimulatio n of vascular factors is sufficient for ulcer healing because epithelial ce lls apparently spontaneously proliferate and migrate over a dense granulati on tissue to complete the healing process. Since these growth factors direc tly stimulate the cell components of ulcer healing, it is probably not surp rising that they are active in both upper and lower GI tract lesions, produ ce good quality of ulcer healing in comparison with spontaneously healed du odenal ulcers which are hypovascular and muscle regeneration is not part of natural healing. Contrary to other antiulcer drugs, these growth factors a re endogenously derived and play a role in the natural history of ulcer hea ling, and since these relatively large peptides (18-45 kDa) are active in n g quantities, their molar potency is 2-7 million times superior to cimetidi ne-like drugs. Thus growth factors are endogenously derived very potent ant iulcer drugs which act independently of GI secretion, are active in upper a nd lower GI lesions, and since they stimulate virtually all the cells of th e healing process, they produce an excellent quality of ulcer healing. (C) 2000 Elsevier Science Ltd. Published by Editions scientifiques et medicales Elsevier SAS.