UVB Induces Sympathetic Nervous System Activation and Norepinephrine Secretion to Regulate The Skin Color of Mice Through the β2-AR/AP-1 Pathway in Epidermal Keratinocytes.

The aim of this study was to investigate how ultraviolet B (UVB) light regulates AP-1 expression via the β2-adrenergic receptor (β2-AR) in epidermal keratinocytes, which in turn regulates melanin synthesis in melanocytes, thereby modulating downstream melanin production in skin hair follicles and altering mouse skin color. We established a UV-irradiated mouse model to investigate the effects of UV radiation on changes in skin color. By measuring changes in the expression of genes related to cutaneous sympathetic nerves, norepinephrine synthesis and melanin synthesis, we investigated the relationship between β2-AR expression and cutaneous melanogenesis and determined the localization of β2-AR in cells. The results of the siRNA-mediated transfection of keratinized cells with downregulated β2-AR expression were further verified in vitro. Our results suggest that UVB alters the color of the dorsal skin in mice by activating the AP-1/IL-6 pathway, which triggers the sympathetic release of norepinephrine, thereby increasing β2-AR expression in keratinocytes. Overall, our study improves the current understanding of how UVB light influences skin color changes and highlights the complex interplay between ultraviolet radiation and skin physiology.