Abstract
The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) transcription factor is a key regulator of the cellular stress response. Therefore, pharmacologic Nrf2 activation is a promising strategy for skin protection and cancer prevention. This study found that genetic Nrf2 activation in keratinocytes accelerates wound repair. Enhanced proliferation of cells of the pilosebaceous unit peripheral to the wound and a concomitant acceleration of re-epithelialization were identified as the underlying mechanism. Nrf2 specifically promoted the expansion of pilosebaceous cells expressing markers of junctional zone and upper isthmus follicular stem cells. This may result, at least in part, from the up-regulation of the direct Nrf2 target epigen and a concomitant increase in epidermal growth factor receptor signaling. The increase in pilosebaceous cells provided a larger pool of keratinocytes that migrate into the wound, resulting in faster wound closure. These results unravel a novel function of Nrf2 in wound repair and suggest the use of NRF2-activating compounds in patients with impaired healing.