Abstract
Migration of human keratinocytes plays a critical role in the re-epithelialization of human skin wounds, the process by which the wound bed is resurfaced and closed by keratinocytes as it forms a new epidermis. While the importance of ECM components and serum factors in the regulation of keratinocytes motility is well established, the intracellular signaling mechanisms remain fragmentary. In this study, we investigated the role of protein kinase Cδ (PKCδ) signaling in the promotion of human keratinocyte migration by a collagen matrix and bovine pituitary extract. We found that pharmacological inhibition of the PKCδ pathway completely blocks migration. Using a lentivirus-based vector system, which offers more than 90% gene transduction efficiency to human keratinocytes, we show that the kinase-defective mutant of PKCδ (K376R) dramatically inhibits human keratinocyte migration. Furthermore, PKCδ is activated in migrating human keratinocytes. These observations indicate for the first time that the PKCδ pathway plays an important role in the control of human keratinocyte migration.
