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Endogenous ω-3 Fatty Acid Production by fat-1 Transgene and Topically Applied Docosahexaenoic Acid Protect against UVB-induced Mouse Skin Carcinogenesis

Cited 11 time in Web of Science Cited 11 time in Scopus
Authors
Yum, Hye-Won; Park, Jin; Park, Hyun-Jung; Shin, Jun Wan; Cho, Yong-Yeon; Kim, Su-Jung; Kang, Jing X.; Surh, Young-Joon
Issue Date
2017-09
Citation
Scientific Reports, Vol.7, p. 11658
Abstract
The present study was intended to explore the effects of endogenously produced omega-3 polyunsaturated fatty acids (PUFAs) on ultraviolet B (UVB)-induced skin inflammation and photocarcinogenesis using hairless fat-1 transgenic mice harboring omega-3 desaturase gene capable of converting omega-6 to omega-3 PUFAs. Upon exposure to UVB irradiation, fat-1 transgenic mice exhibited a significantly reduced epidermal hyperplasia, oxidative skin damage, and photocarcinogenesis as compared to wild type mice. The transcription factor, Nrf2 is a master regulator of anti-inflammatory and antioxidant gene expression. While the protein expression of Nrf2 was markedly enhanced, the level of its mRNA transcript was barely changed in the fat-1 transgenic mouse skin. Topical application of docosahexaenoic acid (DHA), a representative omega-3 PUFA, in wild type hairless mice induced expression of the Nrf2 target protein, heme oxygenase-1 in the skin and protected against UVB-induced oxidative stress, inflammation and papillomagenesis. Furthermore, transient overexpression of fat-1 gene in mouse epidermal JB6 cells resulted in the enhanced accumulation of Nrf2 protein. Likewise, DHA treated to JB6 cells inhibited Nrf2 ubiquitination and stabilized it. Taken together, our results indicate that functional fat-1 and topically applied DHA potentiate cellular defense against UVB-induced skin inflammation and photocarcinogenesis through elevated activation of Nrf2 and upregulation of cytoprotective gene expression.
ISSN
2045-2322
URI
https://hdl.handle.net/10371/172669
DOI
https://doi.org/10.1038/s41598-017-11443-2
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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