C. Sato et al., COMPARATIVE-STUDY OF HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR AND KERATINOCYTE GROWTH-FACTOR EFFECTS ON HUMAN KERATINOCYTES, Journal of investigative dermatology, 104(6), 1995, pp. 958-963
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.