Protective effect of melatonin against blue light‐induced cell damage via the TRPV1–YAP pathway in cultured human epidermal keratinocytes

Although blue light has been known to negatively affect skin cells, its detailed signaling mechanisms and anti-blue light agents have not been clearly elucidated. We investigated the involvement of Yes-associated protein (YAP)-mediated Hippo signaling in blue light-induced apoptosis, depending on the degree of blue light exposure. Additionally, we elucidated the effects of melatonin on blue light-irradiated keratinocytes and examined their action mechanisms. After blue light irradiation, its effects and antagonizing effects of melatonin on cell proliferation, apoptosis, DNA damage, and transient receptor potential vanilloid 1 (TRPV1)/YAP-mediated signaling were examined in HaCaT cells using western blots, image analysis, flow cytometric analysis, co-immunoprecipitation, and immunocytochemistry. We found that melatonin treatment attenuated the reduced cell viability and increased production of reactive oxygen species (ROS) in response to blue light irradiation. In the experiments to investigate the mechanism of action of blue light and melatonin, we found that YAP changed its binding protein, either p73 or TEAD, depending on the degree of blue light exposure. Melatonin treatment reduced blue light-induced phosphorylation of TRPV1 and MST1/2. Upon treatment with capsazepine, an antagonist of TRPV1, MST1/2 activation also reduced. Furthermore, we found that prolonged blue light irradiation induced DNA damage, which in turn induced YAP-p73 nuclear translocation. These effects were also notably attenuated by melatonin. These findings indicate that depending on the duration of blue light irradiation, two different YAP-mediated Hippo signaling pathways are activated. Additionally, these findings suggest that melatonin could be a potential therapeutic agent for blue light-induced skin damage.