Phenotypic variation in the production of bioactive hepatocyte growth factor/scatter factor by oral mucosal and skin fibroblasts

Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic growth factor produced principally by cells of mesenchymal origin. HGF/SF is an important mitogen, morphogen, and motogen and plays an important role in wound healing, tumorigenesis and particularly fetal development. Oral mucosal fibroblasts exhibit a fetal phenotype. including an increased extracellular matrix reorganizational ability, cellular migration and experimental wound repopulation in comparison to skin fibroblasts. In this study the expression, production, and bioactivity of HGF/SF by oral mucosal and skin fibroblasts was investigated. Although both oral mucosal and skin fibroblasts expressed HGF/SF, the oral mucosal fibroblasts produced significantly increased amounts of total HGF/SF (p < 0.01) as measured by enzyme-linked immunosorbent assay and bioactive HGF/SF as measured by cell scatter and cell-dissociation techniques (p < 0.01). The possible effect of increased HGF/SF in production mediating the previously described preferential responses of oral mucosal fibroblasts was studied in vitro. Reverse transcriptase-polymerase chain reaction-Western blotting and immunocytochemistry methods all showed that both oral mucosal and skin fibroblasts expressed and produced the c-Met receptor, Recombinant HGF (20-40 ng/mL) however, failed to affect fibroblast repopulation of monolayer wounds or cellular proliferation. In contrast, recombinant HGF significantly increased ECV304 wound repopulation. These studies provide direct evidence of another mechanism by which site-specific variations in fibroblast phenotype may contribute in a paracrine fashion to the rapid reepithelialization and revascularization of oral wounds.