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

Eun Jung Lee; Ji Young Kim; Yuri Ahn; Byeong min Lee; Yunkyung Heo; Shinwon Hwang; Si Hyung Lee; Jinu Lee; Gehoon Chung; Sang Ho Oh

doi:10.1016/j.jid.2019.02.031

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

Eun Jung Lee, Ji Young Kim, Yuri Ahn, Byeong min Lee, Yunkyung Heo, Shinwon Hwang, Si Hyung Lee, Jinu Lee, Gehoon Chung, Sang Ho Oh

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

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 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.

Original language	English
Pages (from-to)	1554-1563.e6
Journal	Journal of Investigative Dermatology
Volume	139
Issue number	7
DOIs	https://doi.org/10.1016/j.jid.2019.02.031
Publication status	Published - 2019 Jul

Bibliographical note

Funding 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. Conceptualization: GC, SHO; Data Curation: EJL, JYK, BL, YH; Formal Analysis: EJL, JYK, BL; Funding Acquisition: GC, SHO; Investigation: EJL, JYK, BL, YH; Methodology: GC, SHO; Project Administration: SHO; Resources: BL, YH, JL, GC; Supervision: SHO; Validation: EJL, JYK, YA, BL, YH, SH, S-HL, JL, GC, SHO; Visualization: EJL, SHO; Writing – Original Draft: EJL, GC, SHO; Writing – Review & Editing: EJL, SHO

Funding 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.

Publisher Copyright:
© 2019 The Authors

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Biology
Dermatology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jid.2019.02.031

Cite this

@article{4e925e83875d456a9d353772b4c04e93,

title = "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 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.",

author = "Lee, {Eun Jung} and Kim, {Ji Young} and Yuri Ahn and Lee, {Byeong min} and Yunkyung Heo and Shinwon Hwang and Lee, {Si Hyung} and Jinu Lee and Gehoon Chung and Oh, {Sang Ho}",

note = "Funding 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. Conceptualization: GC, SHO; Data Curation: EJL, JYK, BL, YH; Formal Analysis: EJL, JYK, BL; Funding Acquisition: GC, SHO; Investigation: EJL, JYK, BL, YH; Methodology: GC, SHO; Project Administration: SHO; Resources: BL, YH, JL, GC; Supervision: SHO; Validation: EJL, JYK, YA, BL, YH, SH, S-HL, JL, GC, SHO; Visualization: EJL, SHO; Writing – Original Draft: EJL, GC, SHO; Writing – Review & Editing: EJL, SHO Funding 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. Publisher Copyright: {\textcopyright} 2019 The Authors",

year = "2019",

month = jul,

doi = "10.1016/j.jid.2019.02.031",

language = "English",

volume = "139",

pages = "1554--1563.e6",

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T1 - Critical Role of ATP-P2X7 Axis in UV-Induced Melanogenesis

AU - Lee, Eun Jung

AU - Kim, Ji Young

AU - Ahn, Yuri

AU - Lee, Byeong min

AU - Heo, Yunkyung

AU - Hwang, Shinwon

AU - Lee, Si Hyung

AU - Lee, Jinu

AU - Chung, Gehoon

AU - Oh, Sang Ho

N1 - Funding 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. Conceptualization: GC, SHO; Data Curation: EJL, JYK, BL, YH; Formal Analysis: EJL, JYK, BL; Funding Acquisition: GC, SHO; Investigation: EJL, JYK, BL, YH; Methodology: GC, SHO; Project Administration: SHO; Resources: BL, YH, JL, GC; Supervision: SHO; Validation: EJL, JYK, YA, BL, YH, SH, S-HL, JL, GC, SHO; Visualization: EJL, SHO; Writing – Original Draft: EJL, GC, SHO; Writing – Review & Editing: EJL, SHO Funding 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. Publisher Copyright: © 2019 The Authors

PY - 2019/7

Y1 - 2019/7

N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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