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Depletion of peroxiredoxin II promotes keratinocyte apoptosis and alleviates psoriatic skin lesions via the PI3K/AKT/GSK3β signaling axis

Psoriasis is a chronic, systemic immune-mediated disease caused by abnormal proliferation, decreased apoptosis, and over-differentiation of keratinocytes. The psoriatic skin lesions due to abnormal keratinocytes are closely associated with ROS produced by inflammatory cells. Peroxiredoxin II (Prx II...

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Autores principales: Han, Ying-Hao, Feng, Lin, Lee, Seung-Jae, Zhang, Yong-Qing, Wang, Ai-Guo, Jin, Mei-Hua, Sun, Hu-Nan, Kwon, Taeho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10374606/
https://www.ncbi.nlm.nih.gov/pubmed/37500620
http://dx.doi.org/10.1038/s41420-023-01566-z
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author Han, Ying-Hao
Feng, Lin
Lee, Seung-Jae
Zhang, Yong-Qing
Wang, Ai-Guo
Jin, Mei-Hua
Sun, Hu-Nan
Kwon, Taeho
author_facet Han, Ying-Hao
Feng, Lin
Lee, Seung-Jae
Zhang, Yong-Qing
Wang, Ai-Guo
Jin, Mei-Hua
Sun, Hu-Nan
Kwon, Taeho
author_sort Han, Ying-Hao
collection PubMed
description Psoriasis is a chronic, systemic immune-mediated disease caused by abnormal proliferation, decreased apoptosis, and over-differentiation of keratinocytes. The psoriatic skin lesions due to abnormal keratinocytes are closely associated with ROS produced by inflammatory cells. Peroxiredoxin II (Prx II) is an efficient antioxidant enzyme, which were highly expressed in skin tissues of psoriasis patient. However, the detailed mechanical functions of Prx II on psoriatic skin remain to be elucidated. Present study showed that depletion of Prx II results in alleviation of symptoms of IMQ-induced psoriasis in mice, but no significant differences in the amounts of serum inflammatory factors. Prx II-knockdown HaCaT cells were susceptible to H(2)O(2)-induced apoptosis mediated by Ca(2+) release from the endoplasmic reticulum through 1,4,5-triphosphate receptors (IP3Rs), the PI3K/AKT pathway and phosphorylated GSK3β (Ser9) were significant downregulated. Additionally, significantly reduced sensitivity of Prx II-knockdown HaCaT cells to apoptosis was evident post NAC, 2-APB, BAPTA-AM, SC79 and LiCl treated. These results suggest that Prx II regulated apoptosis of keratinocytes via the PI3K/AKT/GSK3β signaling axis. Furthermore, treatment with the Prx II inhibitor Conoidin A significantly alleviated psoriatic symptoms in IMQ model mice. These findings have important implications for developing therapeutic strategies through regulate apoptosis of keratinocytes in psoriasis, and Prx II inhibitors may be exploited as a therapeutic drug to alleviate psoriatic symptoms.
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spelling pubmed-103746062023-07-29 Depletion of peroxiredoxin II promotes keratinocyte apoptosis and alleviates psoriatic skin lesions via the PI3K/AKT/GSK3β signaling axis Han, Ying-Hao Feng, Lin Lee, Seung-Jae Zhang, Yong-Qing Wang, Ai-Guo Jin, Mei-Hua Sun, Hu-Nan Kwon, Taeho Cell Death Discov Article Psoriasis is a chronic, systemic immune-mediated disease caused by abnormal proliferation, decreased apoptosis, and over-differentiation of keratinocytes. The psoriatic skin lesions due to abnormal keratinocytes are closely associated with ROS produced by inflammatory cells. Peroxiredoxin II (Prx II) is an efficient antioxidant enzyme, which were highly expressed in skin tissues of psoriasis patient. However, the detailed mechanical functions of Prx II on psoriatic skin remain to be elucidated. Present study showed that depletion of Prx II results in alleviation of symptoms of IMQ-induced psoriasis in mice, but no significant differences in the amounts of serum inflammatory factors. Prx II-knockdown HaCaT cells were susceptible to H(2)O(2)-induced apoptosis mediated by Ca(2+) release from the endoplasmic reticulum through 1,4,5-triphosphate receptors (IP3Rs), the PI3K/AKT pathway and phosphorylated GSK3β (Ser9) were significant downregulated. Additionally, significantly reduced sensitivity of Prx II-knockdown HaCaT cells to apoptosis was evident post NAC, 2-APB, BAPTA-AM, SC79 and LiCl treated. These results suggest that Prx II regulated apoptosis of keratinocytes via the PI3K/AKT/GSK3β signaling axis. Furthermore, treatment with the Prx II inhibitor Conoidin A significantly alleviated psoriatic symptoms in IMQ model mice. These findings have important implications for developing therapeutic strategies through regulate apoptosis of keratinocytes in psoriasis, and Prx II inhibitors may be exploited as a therapeutic drug to alleviate psoriatic symptoms. Nature Publishing Group UK 2023-07-27 /pmc/articles/PMC10374606/ /pubmed/37500620 http://dx.doi.org/10.1038/s41420-023-01566-z 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 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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Han, Ying-Hao
Feng, Lin
Lee, Seung-Jae
Zhang, Yong-Qing
Wang, Ai-Guo
Jin, Mei-Hua
Sun, Hu-Nan
Kwon, Taeho
Depletion of peroxiredoxin II promotes keratinocyte apoptosis and alleviates psoriatic skin lesions via the PI3K/AKT/GSK3β signaling axis
title Depletion of peroxiredoxin II promotes keratinocyte apoptosis and alleviates psoriatic skin lesions via the PI3K/AKT/GSK3β signaling axis
title_full Depletion of peroxiredoxin II promotes keratinocyte apoptosis and alleviates psoriatic skin lesions via the PI3K/AKT/GSK3β signaling axis
title_fullStr Depletion of peroxiredoxin II promotes keratinocyte apoptosis and alleviates psoriatic skin lesions via the PI3K/AKT/GSK3β signaling axis
title_full_unstemmed Depletion of peroxiredoxin II promotes keratinocyte apoptosis and alleviates psoriatic skin lesions via the PI3K/AKT/GSK3β signaling axis
title_short Depletion of peroxiredoxin II promotes keratinocyte apoptosis and alleviates psoriatic skin lesions via the PI3K/AKT/GSK3β signaling axis
title_sort depletion of peroxiredoxin ii promotes keratinocyte apoptosis and alleviates psoriatic skin lesions via the pi3k/akt/gsk3β signaling axis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10374606/
https://www.ncbi.nlm.nih.gov/pubmed/37500620
http://dx.doi.org/10.1038/s41420-023-01566-z
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