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Article

Upregulated Guanine Deaminase Is Involved in Hyperpigmentation of Seborrheic Keratosis via Uric Acid Release

1
Department of Dermatology, Dongguk University Ilsan Hospital, 814 Siksa-dong, Ilsandong-gu, Goyang-si 410-773, Gyeonggi-do, Korea
2
Basic Research & Innovation Division, Amorepacific Corporation R&D Center, Yongin-si 446-729, Gyeonggi-do, Korea
3
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Genji Imokawa
Int. J. Mol. Sci. 2021, 22(22), 12501; https://doi.org/10.3390/ijms222212501
Received: 13 August 2021 / Revised: 11 November 2021 / Accepted: 16 November 2021 / Published: 19 November 2021
Seborrheic keratosis, which is a benign tumor composed of epidermal keratinocytes, develops common in the elderly. Uric acid generated by upregulated guanine deaminase (GDA) has been identified to cause UV-induced keratinocyte senescence in seborrheic keratosis. Seborrheic keratosis is also frequently pigmented. Growing evidences indicate that hyperuricemia is a risk factor of acanthosis nigricans, an acquired skin hyperpigmentation. The objective of this study was to investigate role of GDA and its metabolic end product, uric acid, in hyperpigmentation of patients with seborrheic keratosis using their lesional and non-lesional skin specimen sets and cultured primary human epidermal keratinocytes with or without GDA overexpression or uric acid treatment. GDA-overexpressing keratinocytes or their conditioned media containing uric acid increased expression levels of MITF and tyrosinase in melanocytes. Uric acid released from keratinocytes was facilitated by ABCG2 transporter with the help of PDZK1 interaction. Released uric acid was taken by URAT1 transporter in melanocytes, stimulating melanogenesis through p38 MAPK activation. Overall, GDA upregulation in seborrheic keratosis plays a role in melanogenesis via its metabolic end product uric acid, suggesting that seborrheic keratosis as an example of hyperpigmentation associated with photoaging. View Full-Text
Keywords: GDA; photoaging; hyperpigmentation; seborrheic keratosis; uric acid GDA; photoaging; hyperpigmentation; seborrheic keratosis; uric acid
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MDPI and ACS Style

Cheong, K.A.; Kil, I.S.; Ko, H.W.; Lee, A.-Y. Upregulated Guanine Deaminase Is Involved in Hyperpigmentation of Seborrheic Keratosis via Uric Acid Release. Int. J. Mol. Sci. 2021, 22, 12501. https://doi.org/10.3390/ijms222212501

AMA Style

Cheong KA, Kil IS, Ko HW, Lee A-Y. Upregulated Guanine Deaminase Is Involved in Hyperpigmentation of Seborrheic Keratosis via Uric Acid Release. International Journal of Molecular Sciences. 2021; 22(22):12501. https://doi.org/10.3390/ijms222212501

Chicago/Turabian Style

Cheong, Kyung A., In S. Kil, Hyuk W. Ko, and Ai-Young Lee. 2021. "Upregulated Guanine Deaminase Is Involved in Hyperpigmentation of Seborrheic Keratosis via Uric Acid Release" International Journal of Molecular Sciences 22, no. 22: 12501. https://doi.org/10.3390/ijms222212501

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