The Pigmentation of Blue Light Is Mediated by Both Melanogenesis Activation and Autophagy Inhibition through OPN3–TRPV1

Blue light, a high-energy radiation in the visible light spectrum, was recently reported to induce skin pigmentation. In this study, we investigated the involvement of TRPV1-mediated signaling along with OPN3 in blue light–induced melanogenesis as well as its signaling pathway. Operating downstream target of OPN3 in blue light–induced melanogenesis, blue light activated TRPV1 and upregulated its expression, resulting in calcium influx. Calcium ion induced the activation of calcium/calmodulin-dependent protein kinase II and MAPK. It also downregulated clusterin expression, leading to the nuclear translocation of PAX3, ultimately affecting melanin synthesis. In addition, blue light interfered with autophagy-mediated regulation of melanosomes by decreasing not only the interaction between clusterin and LC3B but the expression of activating transcription factor family. These findings demonstrate that the pigmenting effects of blue light are mediated by calcium/calmodulin-dependent protein kinase II– and MAPK-mediated signaling as well as clusterin-dependent inhibition of autophagy through OPN3–TRPV1–calcium influx, suggesting, to our knowledge, a previously unreported signaling pathway through which blue light regulates melanocyte biology. Furthermore, these results suggest that TRPV1 and clusterin could be potential therapeutic targets for blue light–induced pigmentation due to prolonged exposure to blue light.