Growth factors in gastrointestinal diseases

This review focuses on the recent investigations demonstrating a pharmacological and pathophysiological role for basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) in ulcerative and inflammatory lesions in the upper and lower gastrointestinal (GI) tract. Our initial experiments revealed that intragastric administration of bFGF-w, acid-resistant bFGF-CS23 and PDGF-BB healed chronic cysteamine (mercaptamine)-induced duodenal ulcer in rats, without decreasing gastric acid secretion or concentration. Subsequently we and others have demonstrated that these peptides accelerate the healing of chronic gastric ulcers, chronic erosive gastritis and ulcerative colitis although they have no or modest acute gastric protective activity. Our recent results revealed a decreased bioactivity of bFGF and PDGF in the presence of certain strains of Helicobacter pylori, and this might explain, at least in part, the poor rates of ulcer healing in H. pylori-positive patients. VEGF, in addition to stimulating angiogenesis and granulation tissue production in duodenal ulcer healing, also has an acute gastroprotective effect. New biochemical, molecular biological and immunohistochemical studies indicate that bFGF, PDGF and VEGF play a pathophysiological role in the natural history of ulcer healing. Thus, growth factor research, especially regarding their possible use as a therapeutic tool in duodenal ulcer and colitis, is challenging. On the other hand, in some GI malignancies the diagnostic use of bFGF might be of clinical benefit. However, much research work is needed to transform these 'endogenous drugs' to 'diagnostic tools' and 'exogenous drugs'.