Activation of Nrf2 in Keratinocytes Causes Chloracne-Like Skin Disease in Mice

Prolonged activation of the transcription factor Nrf2 in keratinocytes led to sebaceous gland enlargement, seborrhea, and hair follicle abnormalities in mice, including thickening, hyperkeratosis, and cyst development, which caused hair loss. The study identified the growth factor epigen as a novel Nrf2 target, along with secretory leukocyte peptidase inhibitor (Slpi) and small proline-rich protein 2d (Sprr2d), which contributed to these skin changes. These findings were similar to the skin condition seen in chloracne/MADISH patients, where SLPI, SPRR2, and epigen were also upregulated in an NRF2-dependent manner. This research highlighted new roles for Nrf2 in the pilosebaceous unit and its potential involvement in MADISH pathogenesis.