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

Area of Science:

• Dermatology
• Molecular Biology
• Skin Aging Research

Background:

• Chronic photodamage from aging causes mottled skin pigmentation and solar lentigines.
• Complex interactions between keratinocytes and melanocytes underlie these skin changes.
• Precise signaling mechanisms for therapeutic targeting remain largely unknown.

Purpose of the Study:

• To investigate the role of nuclear factor erythroid 2-related factor 2 (NRF2) in skin pigmentation.
• To explore NRF2 and IL-6Rα signaling pathways in UV-induced skin damage.
• To evaluate sulforaphane (SF) as a potential therapeutic agent for skin pigmentation.

Main Methods:

• Assessed NRF2 expression in solar lentigines and photodamaged skin.
• Topically applied SF to human skin with mottled pigmentation.
• Utilized UV-exposed mouse ear skin models, including NRF2-deficient and IL-6Rα knockout mice.
• Evaluated SF's efficacy in preventing and treating UV-induced pigmentation.

Main Results:

• NRF2 expression was altered in solar lentigines and photodamaged skin.
• Topical SF treatment reduced mottled skin pigmentation in humans.
• SF treatment prevented and treated UV-induced pigmentation in wild-type mouse ears.
• SF's therapeutic effect was diminished in NRF2-deficient and keratinocyte-specific IL-6Rα knockout mice.

Conclusions:

• NRF2 and IL-6Rα signaling pathways are implicated in the pathogenesis of UV-induced skin pigmentation.
• Targeting NRF2 signaling through enhancement could be a viable therapeutic approach for skin pigmentation disorders.
• Sulforaphane demonstrates potential as a therapeutic agent for photodamaged skin.