MicroRNA-155-5p is a key regulator of allergic inflammation, modulating the epithelial barrier by targeting PKIα
| Autor: | Weiyuan Yuan, Min Hong, Peng Wu, Xiao-Yu Wang, Xiaotong Wang, Lu Yao, Zhirong Jia, Lianqu Li, Yan-Yan Chen, Siqi Wang, Pan Wei |
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| Rok vydání: | 2019 |
| Předmět: |
Cancer Research
medicine.drug_class Immunology Inflammation Occludin Article Dermatitis Atopic Allergic inflammation Mice Cellular and Molecular Neuroscience medicine Animals Humans Gene silencing Secretion lcsh:QH573-671 Protein Kinase Inhibitors Atopic dermatitis Tight junction lcsh:Cytology Chemistry Cell Biology Transfection Protein kinase inhibitor Cell biology Disease Models Animal MicroRNAs medicine.symptom |
| Zdroj: | Cell Death and Disease, Vol 10, Iss 12, Pp 1-14 (2019) Cell Death & Disease |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-019-2124-x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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