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 ex vivo skin cultures. Intracellular calcium ion and protein kinase C/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.
Bibliographical noteFunding Information:
We thank Dong Won Lee and Seung Yong Song (Severance Hospital, Seoul, Korea) for providing postsurgical remnants of human abdominal skin. We are grateful to Vincent Hearing (Pigment Cell Biology Section, National Institutes of Health, Bethesda, MD) for providing MNT1 cell. This study was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) ( NRF- 2016R1C1B2008015 , NRF- 2015R1A1A1A05027503 ) and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare , Republic of Korea (grant number: HI18C0262 ). Also, this work was supported by the Brain Korea 21 PLUS Project for Medical Science, Yonsei University.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology