Epidermal Growth Factor and Insulin-Like Growth Factor I Enhance Keratinocyte Migration

Abstract

Although their mechanisms of action are unclear, a number of growth factors has been shown to promote cutaneous wound repair. Keratinocyte migration and proliferation are required for re-epithelialization, and there is evidence to suggest that these processes may be regulated by one or more growth factors that promote wound repair. Using the phagokinetic assay, which allows direct observation of migration path as a gold-particle-free area, we examined the effects of epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) on human keratinocyte migration. Addition of EGF to defined medium in the absence of any other growth factor induced an increase in migration of 2.5-4.5 fold after overnight incubation; the effect of EGF on migration was concentration dependent, with a maximum at 10 to 50 ng/ml EGF. Concentration-dependent enhancement of keratinocyte migration was similarly observed with IGF-I as well as insulin. With all factors, migration was observed on colloidal gold plates coated with collagen IV or with fibronectin but not in the absence of matrix coating. To examine further the involvement of the EGF receptor in keratinocyte migration, we tested the effect of a monoclonal antibody to the EGF receptor that acts as an antagonist. EGF-induced migration was completely prevented by this antibody; however, the enhancement by insulin or IGF-I was not blocked. These results suggest that IGF-I and insulin enhance keratinocyte migration by a mechanism distinct from that of EGF.