Transcription factor activation in response to cutaneous injury: role of AP-1 in reepithelialization

Reepithelialization is the process responsible for restoring an intact epidermis following cutaneous injury. A change in the activity of keratinocytes is required for reepithelialization to occur, and this is likely to be regulated by the altered expression of effector genes, mediated by transcription factors. The injury itself provides a stimulus for transcription factor activation either directly due to mechanical stress, or via paracrine mechanisms such as the release of growth factors from damaged cells. Members of the activator protein-1 family, in particular c-fos and c-jun, have been the most widely studied wound-induced transcription factors. The signal transduction pathways linking cellular injury to activator protein-1 stimulation appear to involve an increase in intracellular Ca2+ and activation of mitogen-activated protein kinases. Given that a number of genes involved in the reepithelialization of wounds are regulated by activator protein-1, a distinct role for this transcription factor in reepithelialization is beginning to emerge. This article reviews the evidence for activator protein-1 involvement in reepithelialization, with particular focus on the activation of this transcription factor in response to wounding, the second messenger/kinase pathways involved, and the modulation of downstream genes that have the capacity to regulate keratinocyte function.