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Influence of aldo–keto reductase 1C3 polymorphisms in early-onset female psoriasis patients

The principal pathology of psoriasis is impaired skin barrier function, epidermal thickening, and granular layer loss. Exposure to extrinsic factors such as tobacco smoke and air pollutants is associated with the development of psoriasis. Aryl hydrocarbon receptors (AHRs) are activated by extrinsic...

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Autores principales: Nojiri, Yuka, Nakamura, Motoki, Magara, Tetsuya, Yamamoto, Aya, Ikumi, Kyoko, Nakamura, Reiko, Nishida, Emi, Haarmann-Stemmann, Thomas, Morita, Akimichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9968313/
https://www.ncbi.nlm.nih.gov/pubmed/36841845
http://dx.doi.org/10.1038/s41598-023-30464-8
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author Nojiri, Yuka
Nakamura, Motoki
Magara, Tetsuya
Yamamoto, Aya
Ikumi, Kyoko
Nakamura, Reiko
Nishida, Emi
Haarmann-Stemmann, Thomas
Morita, Akimichi
author_facet Nojiri, Yuka
Nakamura, Motoki
Magara, Tetsuya
Yamamoto, Aya
Ikumi, Kyoko
Nakamura, Reiko
Nishida, Emi
Haarmann-Stemmann, Thomas
Morita, Akimichi
author_sort Nojiri, Yuka
collection PubMed
description The principal pathology of psoriasis is impaired skin barrier function, epidermal thickening, and granular layer loss. Exposure to extrinsic factors such as tobacco smoke and air pollutants is associated with the development of psoriasis. Aryl hydrocarbon receptors (AHRs) are activated by extrinsic factors associated with the development of psoriasis and act as transcriptional regulators. Expression of aldo–keto reductase (AKR) 1C3 in the epidermal spinous layer regulates epidermal keratinocyte differentiation via the AHR signaling pathway. We investigated whether single nucleotide polymorphisms (SNPs) in AKR1C3 are associated with the pathogenesis of psoriasis. The proportions of rs12529 G/C, C/C variants, and rs12387 A/A, A/G variants were twofold higher in Japanese psoriasis patients (n = 231) compared with a Japanese healthy cohort. The SNPs were significantly more common than the majority variants in female patients with disease onset ≤ 22 years of age. Patients with rs12529 G > C and rs12387 A > G SNPs exhibited significantly lower AKR1C3 expression and higher expression of late differentiation markers. In conclusion, AKR1C3 downregulation caused by rs12529 G > C and rs12387 A > G SNPs in the epidermis induces abnormal early differentiation of keratinocytes and skin barrier dysfunction, which may contribute to the genetic pathogenesis of psoriasis in young females.
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spelling pubmed-99683132023-02-27 Influence of aldo–keto reductase 1C3 polymorphisms in early-onset female psoriasis patients Nojiri, Yuka Nakamura, Motoki Magara, Tetsuya Yamamoto, Aya Ikumi, Kyoko Nakamura, Reiko Nishida, Emi Haarmann-Stemmann, Thomas Morita, Akimichi Sci Rep Article The principal pathology of psoriasis is impaired skin barrier function, epidermal thickening, and granular layer loss. Exposure to extrinsic factors such as tobacco smoke and air pollutants is associated with the development of psoriasis. Aryl hydrocarbon receptors (AHRs) are activated by extrinsic factors associated with the development of psoriasis and act as transcriptional regulators. Expression of aldo–keto reductase (AKR) 1C3 in the epidermal spinous layer regulates epidermal keratinocyte differentiation via the AHR signaling pathway. We investigated whether single nucleotide polymorphisms (SNPs) in AKR1C3 are associated with the pathogenesis of psoriasis. The proportions of rs12529 G/C, C/C variants, and rs12387 A/A, A/G variants were twofold higher in Japanese psoriasis patients (n = 231) compared with a Japanese healthy cohort. The SNPs were significantly more common than the majority variants in female patients with disease onset ≤ 22 years of age. Patients with rs12529 G > C and rs12387 A > G SNPs exhibited significantly lower AKR1C3 expression and higher expression of late differentiation markers. In conclusion, AKR1C3 downregulation caused by rs12529 G > C and rs12387 A > G SNPs in the epidermis induces abnormal early differentiation of keratinocytes and skin barrier dysfunction, which may contribute to the genetic pathogenesis of psoriasis in young females. Nature Publishing Group UK 2023-02-25 /pmc/articles/PMC9968313/ /pubmed/36841845 http://dx.doi.org/10.1038/s41598-023-30464-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Nojiri, Yuka
Nakamura, Motoki
Magara, Tetsuya
Yamamoto, Aya
Ikumi, Kyoko
Nakamura, Reiko
Nishida, Emi
Haarmann-Stemmann, Thomas
Morita, Akimichi
Influence of aldo–keto reductase 1C3 polymorphisms in early-onset female psoriasis patients
title Influence of aldo–keto reductase 1C3 polymorphisms in early-onset female psoriasis patients
title_full Influence of aldo–keto reductase 1C3 polymorphisms in early-onset female psoriasis patients
title_fullStr Influence of aldo–keto reductase 1C3 polymorphisms in early-onset female psoriasis patients
title_full_unstemmed Influence of aldo–keto reductase 1C3 polymorphisms in early-onset female psoriasis patients
title_short Influence of aldo–keto reductase 1C3 polymorphisms in early-onset female psoriasis patients
title_sort influence of aldo–keto reductase 1c3 polymorphisms in early-onset female psoriasis patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9968313/
https://www.ncbi.nlm.nih.gov/pubmed/36841845
http://dx.doi.org/10.1038/s41598-023-30464-8
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