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Upregulation of ANGPTL6 in mouse keratinocytes enhances susceptibility to psoriasis

Psoriasis is a chronic inflammatory skin disease marked by aberrant tissue repair. Mutant mice modeling psoriasis skin characteristics have provided useful information relevant to molecular mechanisms and could serve to evaluate therapeutic strategies. Here, we found that epidermal ANGPTL6 expressio...

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Autores principales: Tanigawa, Hiroki, Miyata, Keishi, Tian, Zhe, Aoi, Jun, Kadomatsu, Tsuyoshi, Fukushima, Satoshi, Ogata, Aki, Takeda, Naoki, Zhao, Jiabin, Zhu, Shunshun, Terada, Kazutoyo, Endo, Motoyoshi, Morinaga, Jun, Sugizaki, Taichi, Sato, Michio, Morioka, Masaki Suimye, Manabe, Ichiro, Mashimo, Youichi, Hata, Akira, Taketomi, Yoshitaka, Yamamoto, Kei, Murakami, Makoto, Araki, Kimi, Jinnin, Masatoshi, Ihn, Hironobu, Oike, Yuichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5048131/
https://www.ncbi.nlm.nih.gov/pubmed/27698489
http://dx.doi.org/10.1038/srep34690
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author Tanigawa, Hiroki
Miyata, Keishi
Tian, Zhe
Aoi, Jun
Kadomatsu, Tsuyoshi
Fukushima, Satoshi
Ogata, Aki
Takeda, Naoki
Zhao, Jiabin
Zhu, Shunshun
Terada, Kazutoyo
Endo, Motoyoshi
Morinaga, Jun
Sugizaki, Taichi
Sato, Michio
Morioka, Masaki Suimye
Manabe, Ichiro
Mashimo, Youichi
Hata, Akira
Taketomi, Yoshitaka
Yamamoto, Kei
Murakami, Makoto
Araki, Kimi
Jinnin, Masatoshi
Ihn, Hironobu
Oike, Yuichi
author_facet Tanigawa, Hiroki
Miyata, Keishi
Tian, Zhe
Aoi, Jun
Kadomatsu, Tsuyoshi
Fukushima, Satoshi
Ogata, Aki
Takeda, Naoki
Zhao, Jiabin
Zhu, Shunshun
Terada, Kazutoyo
Endo, Motoyoshi
Morinaga, Jun
Sugizaki, Taichi
Sato, Michio
Morioka, Masaki Suimye
Manabe, Ichiro
Mashimo, Youichi
Hata, Akira
Taketomi, Yoshitaka
Yamamoto, Kei
Murakami, Makoto
Araki, Kimi
Jinnin, Masatoshi
Ihn, Hironobu
Oike, Yuichi
author_sort Tanigawa, Hiroki
collection PubMed
description Psoriasis is a chronic inflammatory skin disease marked by aberrant tissue repair. Mutant mice modeling psoriasis skin characteristics have provided useful information relevant to molecular mechanisms and could serve to evaluate therapeutic strategies. Here, we found that epidermal ANGPTL6 expression was markedly induced during tissue repair in mice. Analysis of mice overexpressing ANGPTL6 in keratinocytes (K14-Angptl6 Tg mice) revealed that epidermal ANGPTL6 activity promotes aberrant epidermal barrier function due to hyperproliferation of prematurely differentiated keratinocytes. Moreover, skin tissues of K14-Angptl6 Tg mice showed aberrantly activated skin tissue inflammation seen in psoriasis. Levels of the proteins S100A9, recently proposed as therapeutic targets for psoriasis, also increased in skin tissue of K14-Angptl6 Tg mice, but psoriasis-like inflammatory phenotypes in those mice were not rescued by S100A9 deletion. This finding suggests that decreasing S100A9 levels may not ameliorate all cases of psoriasis and that diverse mechanisms underlie the condition. Finally, we observed enhanced levels of epidermal ANGPTL6 in tissue specimens from some psoriasis patients. We conclude that the K14-Angptl6 Tg mouse is useful to investigate psoriasis pathogenesis and for preclinical testing of new therapeutics. Our study also suggests that ANGPTL6 activation in keratinocytes enhances psoriasis susceptibility.
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spelling pubmed-50481312016-10-11 Upregulation of ANGPTL6 in mouse keratinocytes enhances susceptibility to psoriasis Tanigawa, Hiroki Miyata, Keishi Tian, Zhe Aoi, Jun Kadomatsu, Tsuyoshi Fukushima, Satoshi Ogata, Aki Takeda, Naoki Zhao, Jiabin Zhu, Shunshun Terada, Kazutoyo Endo, Motoyoshi Morinaga, Jun Sugizaki, Taichi Sato, Michio Morioka, Masaki Suimye Manabe, Ichiro Mashimo, Youichi Hata, Akira Taketomi, Yoshitaka Yamamoto, Kei Murakami, Makoto Araki, Kimi Jinnin, Masatoshi Ihn, Hironobu Oike, Yuichi Sci Rep Article Psoriasis is a chronic inflammatory skin disease marked by aberrant tissue repair. Mutant mice modeling psoriasis skin characteristics have provided useful information relevant to molecular mechanisms and could serve to evaluate therapeutic strategies. Here, we found that epidermal ANGPTL6 expression was markedly induced during tissue repair in mice. Analysis of mice overexpressing ANGPTL6 in keratinocytes (K14-Angptl6 Tg mice) revealed that epidermal ANGPTL6 activity promotes aberrant epidermal barrier function due to hyperproliferation of prematurely differentiated keratinocytes. Moreover, skin tissues of K14-Angptl6 Tg mice showed aberrantly activated skin tissue inflammation seen in psoriasis. Levels of the proteins S100A9, recently proposed as therapeutic targets for psoriasis, also increased in skin tissue of K14-Angptl6 Tg mice, but psoriasis-like inflammatory phenotypes in those mice were not rescued by S100A9 deletion. This finding suggests that decreasing S100A9 levels may not ameliorate all cases of psoriasis and that diverse mechanisms underlie the condition. Finally, we observed enhanced levels of epidermal ANGPTL6 in tissue specimens from some psoriasis patients. We conclude that the K14-Angptl6 Tg mouse is useful to investigate psoriasis pathogenesis and for preclinical testing of new therapeutics. Our study also suggests that ANGPTL6 activation in keratinocytes enhances psoriasis susceptibility. Nature Publishing Group 2016-10-04 /pmc/articles/PMC5048131/ /pubmed/27698489 http://dx.doi.org/10.1038/srep34690 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Tanigawa, Hiroki
Miyata, Keishi
Tian, Zhe
Aoi, Jun
Kadomatsu, Tsuyoshi
Fukushima, Satoshi
Ogata, Aki
Takeda, Naoki
Zhao, Jiabin
Zhu, Shunshun
Terada, Kazutoyo
Endo, Motoyoshi
Morinaga, Jun
Sugizaki, Taichi
Sato, Michio
Morioka, Masaki Suimye
Manabe, Ichiro
Mashimo, Youichi
Hata, Akira
Taketomi, Yoshitaka
Yamamoto, Kei
Murakami, Makoto
Araki, Kimi
Jinnin, Masatoshi
Ihn, Hironobu
Oike, Yuichi
Upregulation of ANGPTL6 in mouse keratinocytes enhances susceptibility to psoriasis
title Upregulation of ANGPTL6 in mouse keratinocytes enhances susceptibility to psoriasis
title_full Upregulation of ANGPTL6 in mouse keratinocytes enhances susceptibility to psoriasis
title_fullStr Upregulation of ANGPTL6 in mouse keratinocytes enhances susceptibility to psoriasis
title_full_unstemmed Upregulation of ANGPTL6 in mouse keratinocytes enhances susceptibility to psoriasis
title_short Upregulation of ANGPTL6 in mouse keratinocytes enhances susceptibility to psoriasis
title_sort upregulation of angptl6 in mouse keratinocytes enhances susceptibility to psoriasis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5048131/
https://www.ncbi.nlm.nih.gov/pubmed/27698489
http://dx.doi.org/10.1038/srep34690
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