Hepatocyte growth factor/scatter factor in development, inflammation and carcinogenesis: its expression and role in oral tissues

Hepatocyte growth factor (HGF) was discovered as a potent mitogen for adult hepatocytes from the plasma of patients with fulminant hepatic failure. It is now known to be a broad-spectrum, multi-functional mitogen, motogen and morphogen. The activities of HGF are mediated through the signalling pathway of its receptor, c-Met. During tooth development, HGF is expressed in the dental papilla and c-Met is expressed in the inner enamel epithelium. The expression of HGF and c-Met indicates that HGF is involved in morphogenesis of the tooth by mediating epithelial–mesenchymal interactions. In the mature tooth, HGF expression by fibroblasts is enhanced in pulpitis and mediated through the induction of prostaglandin (PG) E2; it is induced not only by inflammatory cytokines, but also by components of oral bacteria. Consequently, concentrations of HGF in gingival crevicular fluid (GCF) increase in periodontitis. The mitogenic and other biological activities, such as angiogenesis, of HGF contribute towards wound healing. Both HGF and c-Met are expressed in the developing tongue, and the signalling pathway of the latter is shown to be essential for myogenesis. Dysregulation of c-Met signalling is observed in carcinogenesis, but HGF also has cytotoxic activity to certain tumour cells. The reason for the discrepancy between these observations is not clear at present.