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 fa ctor produced principally by cells of mesenchymal origin. HGF/SF is an impo rtant mitogen, morphogen, and motogen and plays an important role in wound healing, tumorigenesis and particularly fetal development. Oral mucosal fib roblasts exhibit a fetal phenotype. including an increased extracellular ma trix reorganizational ability, cellular migration and experimental wound re population 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 expresse d HGF/SF, the oral mucosal fibroblasts produced significantly increased amo unts 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-dissociatio n techniques (p < 0.01). The possible effect of increased HGF/SF in product ion mediating the previously described preferential responses of oral mucos al 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 rec eptor, Recombinant HGF (20-40 ng/mL) however, failed to affect fibroblast r epopulation of monolayer wounds or cellular proliferation. In contrast, rec ombinant HGF significantly increased ECV304 wound repopulation. These studi es provide direct evidence of another mechanism by which site-specific vari ations in fibroblast phenotype may contribute in a paracrine fashion to the rapid reepithelialization and revascularization of oral wounds.