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GPNMB is expressed in human epidermal keratinocytes but disappears in the vitiligo lesional skin

GPNMB is involved in multiple cellular functions including cell adhesion, stress protection and stem cell maintenance. In skin, melanocyte-GPNMB is suggested to mediate pigmentation through melanosome formation, but details of keratinocyte-GPNMB have yet to be well understood. We confirmed the expre...

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Autores principales: Biswas, Kazal Boron, Takahashi, Aya, Mizutani, Yukiko, Takayama, Satoru, Ishitsuka, Asako, Yang, Lingli, Yang, Fei, Iddamalgoda, Arunasiri, Katayama, Ichiro, Inoue, Shintaro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080742/
https://www.ncbi.nlm.nih.gov/pubmed/32188902
http://dx.doi.org/10.1038/s41598-020-61931-1
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author Biswas, Kazal Boron
Takahashi, Aya
Mizutani, Yukiko
Takayama, Satoru
Ishitsuka, Asako
Yang, Lingli
Yang, Fei
Iddamalgoda, Arunasiri
Katayama, Ichiro
Inoue, Shintaro
author_facet Biswas, Kazal Boron
Takahashi, Aya
Mizutani, Yukiko
Takayama, Satoru
Ishitsuka, Asako
Yang, Lingli
Yang, Fei
Iddamalgoda, Arunasiri
Katayama, Ichiro
Inoue, Shintaro
author_sort Biswas, Kazal Boron
collection PubMed
description GPNMB is involved in multiple cellular functions including cell adhesion, stress protection and stem cell maintenance. In skin, melanocyte-GPNMB is suggested to mediate pigmentation through melanosome formation, but details of keratinocyte-GPNMB have yet to be well understood. We confirmed the expression of GPNMB in normal human epidermal keratinocytes (NHEKs) by reducing the expression using siRNA. A higher calcium concentration of over 1.25 mM decreased the GPNMB expression. Histological staining showed that GPNMB was expressed in the basal layer of normal skins but completely absent in vitiligo skins. The normal expression of GPNMB in nevus depigmentosus skin suggested that lack of GPNMB is characteristic of vitiligo lesional skins. IFN-γ and IL-17A, two cytokines with possible causal roles in vitiligo development, inhibited GPNMB expression in vitro. Approximately 4–8% of the total GPNMB expressed on NHEKs were released possibly by ADAM 10 as a soluble form, but the process of release was not affected by the cytokines. The suppressive effect of IFN-γ on GPNMB was partially via IFN-γ/JAK2/STAT1 signaling axis. Decreased GPNMB expression in keratinocytes may affect melanocyte maintenance or survival against oxidative stress although further studies are needed. These findings indicate a new target for vitiligo treatment, focusing on the novel role of IFN-γ and IL-17 in downregulating keratinocyte-GPNMB.
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spelling pubmed-70807422020-03-23 GPNMB is expressed in human epidermal keratinocytes but disappears in the vitiligo lesional skin Biswas, Kazal Boron Takahashi, Aya Mizutani, Yukiko Takayama, Satoru Ishitsuka, Asako Yang, Lingli Yang, Fei Iddamalgoda, Arunasiri Katayama, Ichiro Inoue, Shintaro Sci Rep Article GPNMB is involved in multiple cellular functions including cell adhesion, stress protection and stem cell maintenance. In skin, melanocyte-GPNMB is suggested to mediate pigmentation through melanosome formation, but details of keratinocyte-GPNMB have yet to be well understood. We confirmed the expression of GPNMB in normal human epidermal keratinocytes (NHEKs) by reducing the expression using siRNA. A higher calcium concentration of over 1.25 mM decreased the GPNMB expression. Histological staining showed that GPNMB was expressed in the basal layer of normal skins but completely absent in vitiligo skins. The normal expression of GPNMB in nevus depigmentosus skin suggested that lack of GPNMB is characteristic of vitiligo lesional skins. IFN-γ and IL-17A, two cytokines with possible causal roles in vitiligo development, inhibited GPNMB expression in vitro. Approximately 4–8% of the total GPNMB expressed on NHEKs were released possibly by ADAM 10 as a soluble form, but the process of release was not affected by the cytokines. The suppressive effect of IFN-γ on GPNMB was partially via IFN-γ/JAK2/STAT1 signaling axis. Decreased GPNMB expression in keratinocytes may affect melanocyte maintenance or survival against oxidative stress although further studies are needed. These findings indicate a new target for vitiligo treatment, focusing on the novel role of IFN-γ and IL-17 in downregulating keratinocyte-GPNMB. Nature Publishing Group UK 2020-03-18 /pmc/articles/PMC7080742/ /pubmed/32188902 http://dx.doi.org/10.1038/s41598-020-61931-1 Text en © The Author(s) 2020 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Biswas, Kazal Boron
Takahashi, Aya
Mizutani, Yukiko
Takayama, Satoru
Ishitsuka, Asako
Yang, Lingli
Yang, Fei
Iddamalgoda, Arunasiri
Katayama, Ichiro
Inoue, Shintaro
GPNMB is expressed in human epidermal keratinocytes but disappears in the vitiligo lesional skin
title GPNMB is expressed in human epidermal keratinocytes but disappears in the vitiligo lesional skin
title_full GPNMB is expressed in human epidermal keratinocytes but disappears in the vitiligo lesional skin
title_fullStr GPNMB is expressed in human epidermal keratinocytes but disappears in the vitiligo lesional skin
title_full_unstemmed GPNMB is expressed in human epidermal keratinocytes but disappears in the vitiligo lesional skin
title_short GPNMB is expressed in human epidermal keratinocytes but disappears in the vitiligo lesional skin
title_sort gpnmb is expressed in human epidermal keratinocytes but disappears in the vitiligo lesional skin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080742/
https://www.ncbi.nlm.nih.gov/pubmed/32188902
http://dx.doi.org/10.1038/s41598-020-61931-1
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