期刊
JOURNAL OF DERMATOLOGICAL SCIENCE
卷 90, 期 3, 页码 303-312出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jdermsci.2018.02.016
关键词
Human melanocytes; UVB-induced senescence; Senescence-associated pigmentation; p53; Hyperpigmentation
类别
Background: Ultraviolet radiation (UVR) is a well-known factor in skin aging and pigmentation, and daily exposure to subcytotoxic doses of UVR might accelerate senescence and senescence-associated phenomena in human melanocytes. Objective: To establish an in vitro melanocyte model to mimic the conditions of repeated exposure to subcytotoxic doses of UVB irradiation and to investigate key factor(s) for melanocyte senescence and senescence-associated phenomena. Methods: Human epidermal melanocytes were exposed twice with 20 mJ/cm(2) UVB over a 24-h interval and subsequently cultivated for 2 weeks. Senescent phenotypes were addressed morphologically, and by measuring the senescence-associated beta-galactosidase (SA-beta-Gal) activity, cell proliferation capacity with cell cycle analysis, and melanin content. Results: The established protocol successfully induced melanocyte senescence, and senescent melanocytes accompanied hyperpigmentation. Prolonged expression of p53 was responsible for melanocyte senescence and hyperpigmentation, and treatment with the p53-inhibitor pifithrin-alpha at 2-weeks post-UVB irradiation, but not at 48 h, significantly reduced melanin content along with decreases in tyrosinase levels. Conclusion: Melanocyte senescence model will be useful for studying the long-term effects of UVB irradiation and pigmentation relevant to physiological photoaging, and screening compounds effective for senescence-associated p53-mediated pigmentation. (C) 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
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