Zinc, copper and manganese enhanced keratinocyte migration through a functional modulation of keratinocyte integrins

The migration of keratinocytes plays an important role in the re-epithelialization of cutaneous wounds. Zinc, copper and manganese are used in vivo for their healing properties and their mechanism of action is still only partially known. Thus, they have been shown both to promote keratinocyte proliferation and to modulate integrins expression. The aim of this study was to determine if trace elements induce an increase of the migration of keratinocytes and if this effect is related to the modulation of integrins. Two independent migration assays were used to study keratinocyte migration: the scratch assay using normal human keratinocytes and the modified Boyden chamber using HaCaT cells. Inhibition studies using function-blocking antibodies directed to alpha3, alpha6, alpha(v) and beta1 subunits were performed to investigate the modulator effect of trace elements on integrin function. In this way, zinc and copper gluconates increased alpha3, alpha(v) and beta1 function whereas manganese gluconate seems mainly able to modulate the function of alpha3 and beta1. The stimulating effect of these trace elements on keratinocyte migration does not appear related to alpha6 subunit. Thus, zinc, copper and manganese enhanced keratinocyte migration and one of the mechanisms was going through a modulation of integrin functions.