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

Seborrheic keratosis, which is a benign tumor composed of epidermal keratinocytes, develops common in the elderly. Uric acid generated by upregulated guanine deaminase (<i>GDA</i>) has been identified to cause UV-induced keratinocyte senescence in seborrheic keratosis. Seborrheic keratos...

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Autores principales:	Kyung Ah Cheong, In Sup Kil, Hyuk Wan Ko, Ai-Young Lee
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>GDA</i> photoaging hyperpigmentation seborrheic keratosis uric acid Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/79ddfd26e3474fd5bffd9533f7ba9a9e
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spelling	oai:doaj.org-article:79ddfd26e3474fd5bffd9533f7ba9a9e2021-11-25T17:57:17ZUpregulated Guanine Deaminase Is Involved in Hyperpigmentation of Seborrheic Keratosis via Uric Acid Release10.3390/ijms2222125011422-00671661-6596https://doaj.org/article/79ddfd26e3474fd5bffd9533f7ba9a9e2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12501https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Seborrheic keratosis, which is a benign tumor composed of epidermal keratinocytes, develops common in the elderly. Uric acid generated by upregulated guanine deaminase (<i>GDA</i>) 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 <i>GDA</i> 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 <i>GDA</i> overexpression or uric acid treatment. <i>GDA</i>-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, <i>GDA</i> 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.Kyung Ah CheongIn Sup KilHyuk Wan KoAi-Young LeeMDPI AGarticle<i>GDA</i>photoaginghyperpigmentationseborrheic keratosisuric acidBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12501, p 12501 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>GDA</i> photoaging hyperpigmentation seborrheic keratosis uric acid Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	<i>GDA</i> photoaging hyperpigmentation seborrheic keratosis uric acid Biology (General) QH301-705.5 Chemistry QD1-999 Kyung Ah Cheong In Sup Kil Hyuk Wan Ko Ai-Young Lee Upregulated Guanine Deaminase Is Involved in Hyperpigmentation of Seborrheic Keratosis via Uric Acid Release
description	Seborrheic keratosis, which is a benign tumor composed of epidermal keratinocytes, develops common in the elderly. Uric acid generated by upregulated guanine deaminase (<i>GDA</i>) 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 <i>GDA</i> 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 <i>GDA</i> overexpression or uric acid treatment. <i>GDA</i>-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, <i>GDA</i> 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.
format	article
author	Kyung Ah Cheong In Sup Kil Hyuk Wan Ko Ai-Young Lee
author_facet	Kyung Ah Cheong In Sup Kil Hyuk Wan Ko Ai-Young Lee
author_sort	Kyung Ah Cheong
title	Upregulated Guanine Deaminase Is Involved in Hyperpigmentation of Seborrheic Keratosis via Uric Acid Release
title_short	Upregulated Guanine Deaminase Is Involved in Hyperpigmentation of Seborrheic Keratosis via Uric Acid Release
title_full	Upregulated Guanine Deaminase Is Involved in Hyperpigmentation of Seborrheic Keratosis via Uric Acid Release
title_fullStr	Upregulated Guanine Deaminase Is Involved in Hyperpigmentation of Seborrheic Keratosis via Uric Acid Release
title_full_unstemmed	Upregulated Guanine Deaminase Is Involved in Hyperpigmentation of Seborrheic Keratosis via Uric Acid Release
title_sort	upregulated guanine deaminase is involved in hyperpigmentation of seborrheic keratosis via uric acid release
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/79ddfd26e3474fd5bffd9533f7ba9a9e
work_keys_str_mv	AT kyungahcheong upregulatedguaninedeaminaseisinvolvedinhyperpigmentationofseborrheickeratosisviauricacidrelease AT insupkil upregulatedguaninedeaminaseisinvolvedinhyperpigmentationofseborrheickeratosisviauricacidrelease AT hyukwanko upregulatedguaninedeaminaseisinvolvedinhyperpigmentationofseborrheickeratosisviauricacidrelease AT aiyounglee upregulatedguaninedeaminaseisinvolvedinhyperpigmentationofseborrheickeratosisviauricacidrelease
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Upregulated Guanine Deaminase Is Involved in Hyperpigmentation of Seborrheic Keratosis via Uric Acid Release

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