Nrf2 Activation Enhances Cutaneous Wound Healing by Expansion of Hair Follicle Stem Cell Populations

The study demonstrated that genetic activation of the transcription factor Nrf2 in keratinocytes enhanced cutaneous wound healing by expanding hair follicle stem cell populations, specifically in the junctional zone and upper isthmus. This expansion was mediated by increased EGFR signaling due to up-regulation of the EGF family member Epigen, a direct target of Nrf2. Although Nrf2 activation did not affect proliferation and apoptosis of the wound epithelium or keratinocyte migration in vitro, it increased keratinocyte proliferation and numbers at the wound periphery. The findings suggested that pharmacological activation of Nrf2 could be a promising strategy for improving wound healing by providing a larger pool of keratinocytes to form a longer wound epithelium.