Critical Role of ATP-P2X7 Axis in UV-Induced Melanogenesis

Abstract

Purinergic signaling participates in skin physiology and pathology, such as hair growth, wound healing, inflammation, pain, and skin cancer. However, few studies have investigated the involvement of purinergic signaling in skin pigmentation. This study demonstrated that extracellular adenosine 5'-triphosphate (ATP) released from keratinocytes by UVB radiation promotes melanin production in primary human epidermal melanocytes and exvivo skin cultures. Intracellular calcium ion and protein kinase C/CREB signaling contributed to ATP-mediatedmelanogenesis. Also, P2X7 receptor was proven to play a pivotalrolein ATP-mediatedmelanogenesisbecause P2X7 receptor blockade abrogated ATP-induced melanin production. In addition, MNT1 cells with P2X7 receptor knockout using CRISPR/Cas9 system did not show any increase in MITF expression when co-cultured with UV-irradiated keratinocytes compared to MNT1 cells with intact P2X7 receptor, which showed increased expression of MITF. In conclusion, our results indicate that the extracellularATP-P2X7signalingaxisis an adjunctive mechanism inUV-inducedmelanogenesis. Furthermore, ATP-induced purinergic signaling in melanocytes may alter skin pigmentation.