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MiR-493-5p inhibits Th9 cell differentiation in allergic asthma by targeting FOXO1

The role of micro RNAs (miRNAs) in asthma remains unclear. In this study, we examined the role of miRNA in targeting FOXO1 in asthma. Results showed that miR-493-5p was one of the differentially expressed miRNAs in the PBMCs of asthmatic children, and was also associated with Th cell differentiation...

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Autores principales: Rao, Xingyu, Dong, Heting, Zhang, Weili, Sun, Huiming, Gu, Wenjing, Zhang, Xinxing, Huang, Li, Yan, Yongdong, Hao, Chuangli, Ji, Wei, Zhu, Canhong, Chen, Zhengrong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9578235/
https://www.ncbi.nlm.nih.gov/pubmed/36253857
http://dx.doi.org/10.1186/s12931-022-02207-2
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author Rao, Xingyu
Dong, Heting
Zhang, Weili
Sun, Huiming
Gu, Wenjing
Zhang, Xinxing
Huang, Li
Yan, Yongdong
Hao, Chuangli
Ji, Wei
Zhu, Canhong
Chen, Zhengrong
author_facet Rao, Xingyu
Dong, Heting
Zhang, Weili
Sun, Huiming
Gu, Wenjing
Zhang, Xinxing
Huang, Li
Yan, Yongdong
Hao, Chuangli
Ji, Wei
Zhu, Canhong
Chen, Zhengrong
author_sort Rao, Xingyu
collection PubMed
description The role of micro RNAs (miRNAs) in asthma remains unclear. In this study, we examined the role of miRNA in targeting FOXO1 in asthma. Results showed that miR-493-5p was one of the differentially expressed miRNAs in the PBMCs of asthmatic children, and was also associated with Th cell differentiation. The miR-493-5p expression decreased significantly in the OVA-induced asthma mice than the control groups. The miR-493-5p mimic inhibited the expression of the IL-9, IRF4 and FOXO1, while the inhibitor restored these effects. Moreover, the Dual-Luciferase analysis results showed FOXO1 as a novel valid target of miR-493-5p. According to the rescue experiment, miR-493-5p inhibited Th9 cell differentiation by targeting FOXO1. Then the exosomes in association with the pathogenesis of asthma was identified. Various inflammatory cells implicated in asthmatic processes including B and T lymphocytes, DCs, mast cells, and epithelial cells can release exosomes. Our results demonstrated that the DC-derived exosomes can inhibit Th9 cell differentiation through miR-493-5p, thus DC-derived exosomal miR-493-5p/FOXO1/Th9 may serve as a potential therapeutic target in the development of asthma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-022-02207-2.
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spelling pubmed-95782352022-10-19 MiR-493-5p inhibits Th9 cell differentiation in allergic asthma by targeting FOXO1 Rao, Xingyu Dong, Heting Zhang, Weili Sun, Huiming Gu, Wenjing Zhang, Xinxing Huang, Li Yan, Yongdong Hao, Chuangli Ji, Wei Zhu, Canhong Chen, Zhengrong Respir Res Research The role of micro RNAs (miRNAs) in asthma remains unclear. In this study, we examined the role of miRNA in targeting FOXO1 in asthma. Results showed that miR-493-5p was one of the differentially expressed miRNAs in the PBMCs of asthmatic children, and was also associated with Th cell differentiation. The miR-493-5p expression decreased significantly in the OVA-induced asthma mice than the control groups. The miR-493-5p mimic inhibited the expression of the IL-9, IRF4 and FOXO1, while the inhibitor restored these effects. Moreover, the Dual-Luciferase analysis results showed FOXO1 as a novel valid target of miR-493-5p. According to the rescue experiment, miR-493-5p inhibited Th9 cell differentiation by targeting FOXO1. Then the exosomes in association with the pathogenesis of asthma was identified. Various inflammatory cells implicated in asthmatic processes including B and T lymphocytes, DCs, mast cells, and epithelial cells can release exosomes. Our results demonstrated that the DC-derived exosomes can inhibit Th9 cell differentiation through miR-493-5p, thus DC-derived exosomal miR-493-5p/FOXO1/Th9 may serve as a potential therapeutic target in the development of asthma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-022-02207-2. BioMed Central 2022-10-17 2022 /pmc/articles/PMC9578235/ /pubmed/36253857 http://dx.doi.org/10.1186/s12931-022-02207-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Rao, Xingyu
Dong, Heting
Zhang, Weili
Sun, Huiming
Gu, Wenjing
Zhang, Xinxing
Huang, Li
Yan, Yongdong
Hao, Chuangli
Ji, Wei
Zhu, Canhong
Chen, Zhengrong
MiR-493-5p inhibits Th9 cell differentiation in allergic asthma by targeting FOXO1
title MiR-493-5p inhibits Th9 cell differentiation in allergic asthma by targeting FOXO1
title_full MiR-493-5p inhibits Th9 cell differentiation in allergic asthma by targeting FOXO1
title_fullStr MiR-493-5p inhibits Th9 cell differentiation in allergic asthma by targeting FOXO1
title_full_unstemmed MiR-493-5p inhibits Th9 cell differentiation in allergic asthma by targeting FOXO1
title_short MiR-493-5p inhibits Th9 cell differentiation in allergic asthma by targeting FOXO1
title_sort mir-493-5p inhibits th9 cell differentiation in allergic asthma by targeting foxo1
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9578235/
https://www.ncbi.nlm.nih.gov/pubmed/36253857
http://dx.doi.org/10.1186/s12931-022-02207-2
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