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Publication : Pathogenic and therapeutic role for NRF2 signaling in ultraviolet light-induced skin pigmentation.

First Author  Kerns ML Year  2020
Journal  JCI Insight Volume  5
Issue  20 PubMed ID  33001866
Mgi Jnum  J:329619 Mgi Id  MGI:6717503
Doi  10.1172/jci.insight.139342 Citation  Kerns ML, et al. (2020) Pathogenic and therapeutic role for NRF2 signaling in ultraviolet light-induced skin pigmentation. JCI Insight 5(20)
abstractText  Mottled skin pigmentation and solar lentigines from chronic photodamage with aging involve complex interactions between keratinocytes and melanocytes. However, the precise signaling mechanisms that could serve as therapeutic targets are unclear. Herein, we report that expression of nuclear factor erythroid 2-related factor 2 (NRF2), which regulates reduction-oxidation reactions, is altered in solar lentigines and photodamaged skin. Moreover, mottled skin pigmentation in humans could be treated with topical application of the NRF2 inducer sulforaphane (SF). Similarly, UV light-induced pigmentation of WT mouse ear skin could be treated or prevented with SF treatment. Conversely, SF treatment was unable to reduce UV-induced ear skin pigmentation in mice deficient in NRF2 or in mice with keratinocyte-specific conditional deletion of IL-6Ralpha. Taken together, NRF2 and IL-6Ralpha signaling are involved in the pathogenesis of UV-induced skin pigmentation, and specific enhancement of NRF2 signaling could represent a potential therapeutic target.
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