Journal of photochemistry and photobiology. B, Biology · 2025
UVB enhances SLC6A15-mediated phenylalanine transport to promote melanogenesis.
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Zhou Shu, Ouyang Yujie, Hu Yibo, Dai Xixia, Jiang Ling, Fu Chuhan, Wen Yaqing, Huang Jiangfeng, Zhang Keyi, Chen Jing, Zeng Qinghai
Аннотация
BACKGROUND: Abnormal melanogenesis is a fundamental biological process underlying pigmentary disorders. While several solute carrier (SLC) transporters have been implicated in its regulation, the functions of many SLCs members remain poorly characterized.
METHODS: We delineated transcriptional features of melanocytes with high melanogenic activity using single-cell and bulk RNA sequencing. Key SLC genes associated with melanogenesis were identified and prioritized using machine learning and Mendelian randomization analyses, followed by in vitro functional validation.
RESULTS: Integrated multi-omics analysis identified SLC6A15 as a potential regulator of melanogenesis. SLC6A15 knockdown in MNT1 cells and primary melanocytes reduced melanin synthesis and downregulated key melanogenesis-related genes (e.g., MITF, TYR, DCT). Fontana-Masson staining and tyrosinase activity assays confirmed a marked decrease in melanin deposition and TYR activity in SLC6A15-depleted cells. UVB exposure upregulated SLC6A15, whereas SLC6A15 silencing abrogated the UVB-induced increase in pigmentation. Mechanistically, SLC6A15 knockdown reduced intracellular phenylalanine levels, indicating a role for SLC6A15-mediated phenylalanine transport in melanogenesis. Mendelian randomization further suggested that genetically higher phenylalanine levels are associated with an increased risk of melasma (OR = 6.02).
CONCLUSIONS: Our findings identify SLC6A15 as a potential key regulator of melanogenesis through the transport of phenylalanine.
METHODS: We delineated transcriptional features of melanocytes with high melanogenic activity using single-cell and bulk RNA sequencing. Key SLC genes associated with melanogenesis were identified and prioritized using machine learning and Mendelian randomization analyses, followed by in vitro functional validation.
RESULTS: Integrated multi-omics analysis identified SLC6A15 as a potential regulator of melanogenesis. SLC6A15 knockdown in MNT1 cells and primary melanocytes reduced melanin synthesis and downregulated key melanogenesis-related genes (e.g., MITF, TYR, DCT). Fontana-Masson staining and tyrosinase activity assays confirmed a marked decrease in melanin deposition and TYR activity in SLC6A15-depleted cells. UVB exposure upregulated SLC6A15, whereas SLC6A15 silencing abrogated the UVB-induced increase in pigmentation. Mechanistically, SLC6A15 knockdown reduced intracellular phenylalanine levels, indicating a role for SLC6A15-mediated phenylalanine transport in melanogenesis. Mendelian randomization further suggested that genetically higher phenylalanine levels are associated with an increased risk of melasma (OR = 6.02).
CONCLUSIONS: Our findings identify SLC6A15 as a potential key regulator of melanogenesis through the transport of phenylalanine.