KERATINOCYTE GROWTH-FACTOR (FGF-7) STIMULATES MIGRATION AND PLASMINOGEN-ACTIVATOR ACTIVITY OF NORMAL HUMAN KERATINOCYTES

Keratinocyte growth factor (KGF), a member of the fibroblast growth fa ctor (FGF) family (and alternatively designated FGF-7), is a paracrine growth factor produced by mesenchymal cells and mitogenic specificall y for epithelial cells. The potential effect of KGF on wound healing w as assessed in vitro by measuring randomized migration and plasminogen activator (PA) activity of keratinocytes in response to the growth fa ctor. Incubation of normal human keratinocytes with KGF in modified MC DB 153 medium significantly stimulated cell migration and PA activity compared with control (p < 0.001 and p < 0.01, respectively). When tes ted in these assays on an equimolar basis, 1 nM KGF was at least as po tent as transforming growth factor alpha and more active than basic FG F. None of these effects were observed when KGF was administered to fi broblasts or endothelial cells. Stimulation of keratinocyte migration by KGF was dose dependent, and a neutralizing monoclonal antibody agai nst KGF reduced KGF-stimulated migration and cell growth. Zymographic analyses of cell extracts and conditioned medium from KGF-treated kera tinocytes revealed increased PA activity, which was mainly attributabl e to an elevated level of urokinase-type PA. These in vitro results su ggest that KGF may have an important role in stimulating reepitheliali zation during the process of wound repair.