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• W2884371609 abstract "The major modifiable risk factor in melanomagenesis is UV exposure and mutagenesis of melanocytes. Other UV-induced events that contribute to early tumorigenesis are poorly understood. Herein we show that the repeated exposure of human primary melanocytes to UVB results in a sustained senescence response, increases in expression of signal transducer and activator of transcription 1, MX1, OAS2, and IRF7 proteins of up to 75-fold, and resistance to subsequent UVB-induced apoptosis. In the setting of UVB-induced DNA damage, we detected time-dependent increases in the release of damage-associated molecular patterns such as high-mobility group box 1 (HMGB1). After intermittent UVB exposure, melanocytes treated with the JAK inhibitor ruxolitinib reduced expression of HMGB1 and MX1 as well as activation of JAK1 (pJAK1) and signal transducer and activator of transcription 1 (pSTAT1). In addition, melanocytes expressing small hairpin RNA selective for the HMGB1 receptor, receptor for advanced glycosylation end product (RAGE), exhibited decreased expression of both HMGB1 and MX1 after UVB exposure. The response of small hairpin RAGE-infected cells to human recombinant HMGB1 was blunted with decreased MX1 expression and JAK activation. Finally, depletion of receptor for advanced glycosylation end product decreased UVB-induced resistance to apoptosis (P < 0.05). These findings highlight a cell autonomous response to UV damage, contribute to their resistance to apoptosis and cell death, and may have implications for early stages of melanoma development." @default.
• W2884371609 created "2018-08-03" @default.
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• W2884371609 date "2019-01-01" @default.
• W2884371609 modified "2023-10-18" @default.
• W2884371609 title "HMGB1/RAGE Mediates UVB-Induced Secretory Inflammatory Response and Resistance to Apoptosis in Human Melanocytes" @default.
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• W2884371609 doi "https://doi.org/10.1016/j.jid.2018.05.035" @default.
• W2884371609 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30030153" @default.
• W2884371609 hasPublicationYear "2019" @default.
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