COMPARATIVE-STUDY OF HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR AND KERATINOCYTE GROWTH-FACTOR EFFECTS ON HUMAN KERATINOCYTES

Hepatocyte growth factor/scatter factor (HGF/SF) and keratinocyte grow th factor (KGF, also designated FGF-7) are paracrine growth factors se creted by mesenchymal cells and active on a variety of epithelial cell types. In this study, the biologic responses of keratinocytes to thes e paracrine growth factors were compared. Stimulation of mitogenesis, migration, plasminogen activator (PA) activity, and fibronectin produc tion were examined using human foreskin keratinocytes cultured in seru m-free MCDB 153 medium. Although the two factors stimulated a similar level of proliferation when cells were maintained for 5 d in 1.8 mM Ca ++, the peak effect of KGF, observed at 10 ng/ml, was approximately th reefold higher than that of HGF/SF when cells were in medium containin g 0.15 mM Ca++. Both agents promoted the migration of cells in few-cal cium medium (0.08 mM Ca++). However, the magnitude of the response was approximately twofold greater for HGF/SF at 10 ng/ml than KGF at the same concentration. None of the matrix proteins such as type I collage n, type IV collagen, laminin, or fibronectin either stimulated or supp ressed HGF/SF- or KGF-stimulated keratinocyte migration. Both factors stimulated PA activity of the cell extracts, especially urokinase-type , with similar potencies. Promoted PA activity was maximal with the ad dition of 10 ng/ml of either factor. Neither factor increased the prod uction of fibronectin under conditions in which transforming growth fa ctor-beta 1 was active. These results indicate that HGF/SF and KGF, bo th recognized as paracrine growth factors, elicit distinctive patterns of response by keratinocytes, implying that they have different roles in epidermal physiology.