Mechanisms of Skin Cell Migration and Wound Healing

Skin cell migration is essential for skin wound healing. Steps for cell migration are often disrupted in non-healing wounds, causing patient morbidity. Currently-available treatments are unsatisfactory. To identify novel wound-healing targets, we studied the migratory gene profiles in human keratinocytes (HKs). The main challenge of this study is to separate genes that are often simultaneously induced by pleiotropic signals of a growth factor, including migration, proliferation and metabolism. Therefore, we designed the following steps. First, we took advantage of a unique response of HKs to TGF-beta, which inhibits proliferation but not migration of the cells, to suppress selectively the proliferation signal-responding genes. Second, we independently stimulated HKs with TGF-alpha or insulin to identify the commonly regulated genes and eliminate TGF-alpha- or insulin-specific genes. Under these designs, we obtained the profiles of early genes by microarray analyses, followed by QRT-PCR validation and subsequently functional characterizations by RNAi. The study suggested the importance of secretory molecules in keratinocyte migration.