Growth factors such as
epidermal growth factor (
EGF),
basic fibroblast growth factor (bFGF),
platelet-derived growth factor (PDGF) and more recently
vascular endothelial growth factor (
VEGF) have been used extensively to heal experimental gastric, duodenal and colonic
ulcers in animal models. Encouraging results have been reported in clinical trials with
EGF and bFGF. Since our laboratory has been involved with the initial
ulcer healing studies with bFGF, PDGF and
VEGF, we summarize here the major lessons from these studies and from literature data. These conclusions relate to the role of: 1) gastrointestinal (GI) secretion; 2) epithelial versus vascular components of the healing; 3) efficacy in the upper and lower GI tract; 4) quality of
ulcer healing; as well as 5) the endogenous origin; and 6) molar potency of
growth factors. Namely, among these
growth factors only
EGF inhibits gastric acid and stimulates duodenal
bicarbonate secretion, while chronic administration 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 these
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 >> PDGF >>
EGF. Conceptually, the most interesting results were obtained recently with
VEGF which is virtually specific for angiogenesis, illustrating that stimulation of vascular factors is sufficient for
ulcer healing because epithelial cells apparently spontaneously proliferate and migrate over a dense granulation tissue to complete the healing process. Since these
growth factors directly stimulate the cell components of
ulcer healing, it is probably not surprising that they are active in both upper and lower GI tract lesions, produce good quality of
ulcer healing in comparison with spontaneously healed
duodenal ulcers which are hypovascular and muscle regeneration is not part of natural healing. Contrary to other antiulcer drugs, these
growth factors are endogenously derived and play a role in the natural history of
ulcer healing, and since these relatively large
peptides (18-45 kDa) are active in ng quantities, their molar potency is 2-7 million times superior to
cimetidine-like drugs. Thus
growth factors are endogenously derived very potent antiulcer drugs which act independently of GI secretion, are active in upper and lower GI lesions, and since they stimulate virtually all the cells of the healing process, they produce an excellent quality of
ulcer healing.