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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 ultraviolet B (UVB) radiation promotes melanin production in primary human epidermal melanocytes and ex vivo skin cultures. Intracellular calcium ion and protein kinase C (PKC)/cAMP response element-binding protein (CREB) signaling contributed to ATP-mediated melanogenesis. Also, P2X7 receptor was proven to play a pivotal role in ATP-mediated melanogenesis because 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 extracellular ATP-P2X7 signaling axis is an adjunctive mechanism in UV-induced melanogenesis. Furthermore, ATP-induced purinergic signaling in melanocytes may alter skin pigmentation.

Author information

Lee EJ1, Kim JY2, Ahn Y2, Lee BM3, Heo Y4, Hwang S2, Lee SH5, Lee J4, Chung G6, Oh SH7.
1
Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
2
Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
3
Department of Oral Physiology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Korea.
4
College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Korea.
5
Department of Dermatology, Seoul National University Hospital, Seoul, Korea.
6
Department of Oral Physiology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Korea. Electronic address: oddung93@yuhs.ac.
7
Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. Electronic address: oddung93@yuhs.ac.