A Role for NRF2-Signaling in the Treatment and Prevention of Solar Lentigines
| Autor: | Sewon Kang, Michelle L. Kerns, Anna L. Chien |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
NF-E2-Related Factor 2 Ultraviolet Rays Photoaging medicine.disease_cause Skin Aging Pathogenesis Mice chemistry.chemical_compound Isothiocyanates Animals Humans Medicine Broccoli sprout extract Receptor Aged Lentigo integumentary system Plant Extracts business.industry Middle Aged medicine.disease Hyperpigmentation Mice Inbred C57BL chemistry Sulfoxides Models Animal Cancer research Surgery medicine.symptom business Oxidative stress Sulforaphane |
| Zdroj: | Plastic & Reconstructive Surgery. 148:27S-31S |
| ISSN: | 0032-1052 |
| DOI: | 10.1097/prs.0000000000008783 |
| Popis: | Background Photoaging is premature skin aging resulting from oxidative stress generated by exposure to solar radiation. A key clinical feature is solar lentigines, areas of hyperpigmentation on sun-exposed skin. Skin pigmentation is determined by cross-talk between keratinocytes and melanocytes, which is exquisitely sensitive to oxidative stress. Toll-like receptor (TLR) signaling and NF-E2-related factor 2 (NRF2) signaling, an endogenous antioxidant system, serve as a bridge between the oxidative stress response and immune regulation. Moreover, TLR-mediated induction of IL-6 production has been shown to prevent ultraviolet (UV)-induced hyperpigmentation. Methods Shave biopsies of solar lentigines were obtained from 14 individuals. An additional 7 subjects applied broccoli sprout extract (BSE) containing sulforaphane daily or vehicle on photodamaged skin. Immunofluorescence staining was used to determine total and phosphorylated NRF2 in the lentiginous skin. Dermoscopy and Fontana & Masson staining were used to assess the effect of topical BSE on UV-induced pigmentation. Similar topical treatments were performed in a mouse model of UVB-induced hyperpigmentation utilizing WT, Nrf2-/-, or K14-Cre-ERT2IL-6Rαfl/fl C57BL/6 mice. Results NRF2 expression is altered in solar lentigines, and UV-induced skin pigmentation in humans could be ameliorated with topical BSE. Corresponding mouse models replicated the authors' clinical findings and identified a potential mechanistic link to IL-6Rα signaling in keratinocytes. Conclusion The authors' findings suggest that dysregulation of NRF2 signaling is involved in the pathogenesis of UV-induced skin pigmentation and pharmacological activation of NRF2 may represent a potential therapeutic target in photoaging. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|