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MicroRNA-155-5p is a key regulator of allergic inflammation, modulating the epithelial barrier by targeting PKIα

Recent studies have demonstrated that microRNA-155-5p (miR-155-5p) plays an essential role in the regulation of allergen-induced inflammation and is overexpressed in the skin of patients with atopic dermatitis (AD), although the mechanism is unknown. In this study, silencing miR-155-5p attenuated th...

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Autores principales: Wang, Xiaoyu, Chen, Yanyan, Yuan, Weiyuan, Yao, Lu, Wang, Siqi, Jia, Zhirong, Wu, Peng, Li, Lianqu, Wei, Pan, Wang, Xiaotong, Hong, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6877533/
https://www.ncbi.nlm.nih.gov/pubmed/31767859
http://dx.doi.org/10.1038/s41419-019-2124-x
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author Wang, Xiaoyu
Chen, Yanyan
Yuan, Weiyuan
Yao, Lu
Wang, Siqi
Jia, Zhirong
Wu, Peng
Li, Lianqu
Wei, Pan
Wang, Xiaotong
Hong, Min
author_facet Wang, Xiaoyu
Chen, Yanyan
Yuan, Weiyuan
Yao, Lu
Wang, Siqi
Jia, Zhirong
Wu, Peng
Li, Lianqu
Wei, Pan
Wang, Xiaotong
Hong, Min
author_sort Wang, Xiaoyu
collection PubMed
description Recent studies have demonstrated that microRNA-155-5p (miR-155-5p) plays an essential role in the regulation of allergen-induced inflammation and is overexpressed in the skin of patients with atopic dermatitis (AD), although the mechanism is unknown. In this study, silencing miR-155-5p attenuated the thickening of the epidermis in AD model and reduced the infiltration of inflammatory cells and the secretion of Th2 cytokines. Protein kinase inhibitor α (PKIα) was identified as a direct target of miR-155-5p and correlated negatively with miR-155-5p in our AD model. Fluorescence in situ hybridization showed that miR-155-5p-expressing cells were predominantly present in the epidermis. When epithelial cells were transfected with an miR-155-5p inhibitor, the expression of PKIα, occludin, and CLDN16 increased and that of TSLP decreased significantly, whereas the overexpression of miR-155-5p resulted in the opposite changes. The increased expression of PKIα and tight junction (TJ) proteins, with reduced TSLP and IL-33, was also detected in miR-155-5p-blocked mice, in both the initial and elicitation stages of AD. The expression of TJ proteins also decreased when cells were transfected with PKIα siRNA. TJ proteins increased and TSLP and IL-33 decreased significantly after the overexpression of PKIα. Our data provide the first evidence that miR-155-5p is critical for the allergic inflammation in a mouse model of AD by directly regulating PKIα and thus epithelial TJ expression. These findings suggest new therapeutic strategies that target miR-155-5p in patients with allergic disorders.
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spelling pubmed-68775332019-11-26 MicroRNA-155-5p is a key regulator of allergic inflammation, modulating the epithelial barrier by targeting PKIα Wang, Xiaoyu Chen, Yanyan Yuan, Weiyuan Yao, Lu Wang, Siqi Jia, Zhirong Wu, Peng Li, Lianqu Wei, Pan Wang, Xiaotong Hong, Min Cell Death Dis Article Recent studies have demonstrated that microRNA-155-5p (miR-155-5p) plays an essential role in the regulation of allergen-induced inflammation and is overexpressed in the skin of patients with atopic dermatitis (AD), although the mechanism is unknown. In this study, silencing miR-155-5p attenuated the thickening of the epidermis in AD model and reduced the infiltration of inflammatory cells and the secretion of Th2 cytokines. Protein kinase inhibitor α (PKIα) was identified as a direct target of miR-155-5p and correlated negatively with miR-155-5p in our AD model. Fluorescence in situ hybridization showed that miR-155-5p-expressing cells were predominantly present in the epidermis. When epithelial cells were transfected with an miR-155-5p inhibitor, the expression of PKIα, occludin, and CLDN16 increased and that of TSLP decreased significantly, whereas the overexpression of miR-155-5p resulted in the opposite changes. The increased expression of PKIα and tight junction (TJ) proteins, with reduced TSLP and IL-33, was also detected in miR-155-5p-blocked mice, in both the initial and elicitation stages of AD. The expression of TJ proteins also decreased when cells were transfected with PKIα siRNA. TJ proteins increased and TSLP and IL-33 decreased significantly after the overexpression of PKIα. Our data provide the first evidence that miR-155-5p is critical for the allergic inflammation in a mouse model of AD by directly regulating PKIα and thus epithelial TJ expression. These findings suggest new therapeutic strategies that target miR-155-5p in patients with allergic disorders. Nature Publishing Group UK 2019-11-25 /pmc/articles/PMC6877533/ /pubmed/31767859 http://dx.doi.org/10.1038/s41419-019-2124-x Text en © The Author(s) 2019 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
Wang, Xiaoyu
Chen, Yanyan
Yuan, Weiyuan
Yao, Lu
Wang, Siqi
Jia, Zhirong
Wu, Peng
Li, Lianqu
Wei, Pan
Wang, Xiaotong
Hong, Min
MicroRNA-155-5p is a key regulator of allergic inflammation, modulating the epithelial barrier by targeting PKIα
title MicroRNA-155-5p is a key regulator of allergic inflammation, modulating the epithelial barrier by targeting PKIα
title_full MicroRNA-155-5p is a key regulator of allergic inflammation, modulating the epithelial barrier by targeting PKIα
title_fullStr MicroRNA-155-5p is a key regulator of allergic inflammation, modulating the epithelial barrier by targeting PKIα
title_full_unstemmed MicroRNA-155-5p is a key regulator of allergic inflammation, modulating the epithelial barrier by targeting PKIα
title_short MicroRNA-155-5p is a key regulator of allergic inflammation, modulating the epithelial barrier by targeting PKIα
title_sort microrna-155-5p is a key regulator of allergic inflammation, modulating the epithelial barrier by targeting pkiα
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6877533/
https://www.ncbi.nlm.nih.gov/pubmed/31767859
http://dx.doi.org/10.1038/s41419-019-2124-x
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