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IL-13 Regulates Orai1 Expression in Human Bronchial Smooth Muscle Cells and Airway Remodeling in Asthma Mice Model via LncRNA H19
BACKGROUND: Increased proliferation and hypertrophy of airway smooth muscle cells (ASMCs) contribute substantially to airway remodeling in asthma. Interleukin (IL)-13 regulates ASMC proliferation by increasing Orai1 expression, the pore-forming subunit of store-operated Ca(2+) entry (SOCE). The unde...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9464454/ https://www.ncbi.nlm.nih.gov/pubmed/36101840 http://dx.doi.org/10.2147/JAA.S360381 |
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author | Xiang, Lin-Li Wan, Qian-Qian Wang, Yi-Min He, Shao-Jun Xu, Wen-Juan Ding, Mei Zhang, Jin-Jin Sun, Yuan-Li Dong, Xiang Zhou, Ying Cui, Yu-Bao Gao, Ya-Dong |
author_facet | Xiang, Lin-Li Wan, Qian-Qian Wang, Yi-Min He, Shao-Jun Xu, Wen-Juan Ding, Mei Zhang, Jin-Jin Sun, Yuan-Li Dong, Xiang Zhou, Ying Cui, Yu-Bao Gao, Ya-Dong |
author_sort | Xiang, Lin-Li |
collection | PubMed |
description | BACKGROUND: Increased proliferation and hypertrophy of airway smooth muscle cells (ASMCs) contribute substantially to airway remodeling in asthma. Interleukin (IL)-13 regulates ASMC proliferation by increasing Orai1 expression, the pore-forming subunit of store-operated Ca(2+) entry (SOCE). The underlying mechanisms of this effect are not fully understood. METHODS: Bioinformatic analysis identified an interaction between microRNA 93–5p (miR-93-5p) and long non-coding RNA (lncRNA) H19, and between miR-93-5p and Orai1. RNA interference was used to investigate H19 knockdown on IL-13-induced proliferation and migration of in vitro cultured human bronchial smooth muscle cells (hBSMCs). Functional relevance of H19 in airway inflammation and airway remodeling was investigated in murine models of acute and chronic asthma. RESULTS: IL-13 concentration-dependently increased the expression of H19 and Orai1 and decreased the expression of miR-93-5p in hBSMCs. H19 knockdown partly reversed the effects of IL-13 on the expression of miR-93-5p and Orai1 and attenuated the proliferation and migration of hBSMCs promoted by IL-13. IL-13-promoted expression of Orai1 was attenuated by miR-93-5p mimic and increased by miR-93-5p inhibitor. IL-13-promoted proliferation of hBSMCs was increased by miR-93-5p inhibitor but not affected by miR-93-5p mimic, whereas IL-13-promoted migration of hBSMCs was increased by miR-93-5p inhibitor and attenuated by miR-93-5p mimic. The inhibiting effect of H19 knockdown on IL-13-induced Orai1 expression and the proliferation and migration of hBSMCs was counteracted by miR-93-5p inhibitor but only marginally or not impacted by miR-93-5p mimic. The expression of H19 and Orai1 was higher in the lungs of asthmatic mice than in control mice. In asthmatic mice, H19 siRNA reduced Orai1 expression, inflammatory cell infiltration, goblet cell hyperplasia, collagen deposition and smooth muscle mass in the lungs. CONCLUSION: H19 may mediate the effects of IL-13 on Orai1 expression by inhibition of miR-93-5p in hBSMCs. H19 may be a therapeutic target for airway inflammation and airway remodeling. |
format | Online Article Text |
id | pubmed-9464454 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-94644542022-09-12 IL-13 Regulates Orai1 Expression in Human Bronchial Smooth Muscle Cells and Airway Remodeling in Asthma Mice Model via LncRNA H19 Xiang, Lin-Li Wan, Qian-Qian Wang, Yi-Min He, Shao-Jun Xu, Wen-Juan Ding, Mei Zhang, Jin-Jin Sun, Yuan-Li Dong, Xiang Zhou, Ying Cui, Yu-Bao Gao, Ya-Dong J Asthma Allergy Original Research BACKGROUND: Increased proliferation and hypertrophy of airway smooth muscle cells (ASMCs) contribute substantially to airway remodeling in asthma. Interleukin (IL)-13 regulates ASMC proliferation by increasing Orai1 expression, the pore-forming subunit of store-operated Ca(2+) entry (SOCE). The underlying mechanisms of this effect are not fully understood. METHODS: Bioinformatic analysis identified an interaction between microRNA 93–5p (miR-93-5p) and long non-coding RNA (lncRNA) H19, and between miR-93-5p and Orai1. RNA interference was used to investigate H19 knockdown on IL-13-induced proliferation and migration of in vitro cultured human bronchial smooth muscle cells (hBSMCs). Functional relevance of H19 in airway inflammation and airway remodeling was investigated in murine models of acute and chronic asthma. RESULTS: IL-13 concentration-dependently increased the expression of H19 and Orai1 and decreased the expression of miR-93-5p in hBSMCs. H19 knockdown partly reversed the effects of IL-13 on the expression of miR-93-5p and Orai1 and attenuated the proliferation and migration of hBSMCs promoted by IL-13. IL-13-promoted expression of Orai1 was attenuated by miR-93-5p mimic and increased by miR-93-5p inhibitor. IL-13-promoted proliferation of hBSMCs was increased by miR-93-5p inhibitor but not affected by miR-93-5p mimic, whereas IL-13-promoted migration of hBSMCs was increased by miR-93-5p inhibitor and attenuated by miR-93-5p mimic. The inhibiting effect of H19 knockdown on IL-13-induced Orai1 expression and the proliferation and migration of hBSMCs was counteracted by miR-93-5p inhibitor but only marginally or not impacted by miR-93-5p mimic. The expression of H19 and Orai1 was higher in the lungs of asthmatic mice than in control mice. In asthmatic mice, H19 siRNA reduced Orai1 expression, inflammatory cell infiltration, goblet cell hyperplasia, collagen deposition and smooth muscle mass in the lungs. CONCLUSION: H19 may mediate the effects of IL-13 on Orai1 expression by inhibition of miR-93-5p in hBSMCs. H19 may be a therapeutic target for airway inflammation and airway remodeling. Dove 2022-09-07 /pmc/articles/PMC9464454/ /pubmed/36101840 http://dx.doi.org/10.2147/JAA.S360381 Text en © 2022 Xiang et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Xiang, Lin-Li Wan, Qian-Qian Wang, Yi-Min He, Shao-Jun Xu, Wen-Juan Ding, Mei Zhang, Jin-Jin Sun, Yuan-Li Dong, Xiang Zhou, Ying Cui, Yu-Bao Gao, Ya-Dong IL-13 Regulates Orai1 Expression in Human Bronchial Smooth Muscle Cells and Airway Remodeling in Asthma Mice Model via LncRNA H19 |
title | IL-13 Regulates Orai1 Expression in Human Bronchial Smooth Muscle Cells and Airway Remodeling in Asthma Mice Model via LncRNA H19 |
title_full | IL-13 Regulates Orai1 Expression in Human Bronchial Smooth Muscle Cells and Airway Remodeling in Asthma Mice Model via LncRNA H19 |
title_fullStr | IL-13 Regulates Orai1 Expression in Human Bronchial Smooth Muscle Cells and Airway Remodeling in Asthma Mice Model via LncRNA H19 |
title_full_unstemmed | IL-13 Regulates Orai1 Expression in Human Bronchial Smooth Muscle Cells and Airway Remodeling in Asthma Mice Model via LncRNA H19 |
title_short | IL-13 Regulates Orai1 Expression in Human Bronchial Smooth Muscle Cells and Airway Remodeling in Asthma Mice Model via LncRNA H19 |
title_sort | il-13 regulates orai1 expression in human bronchial smooth muscle cells and airway remodeling in asthma mice model via lncrna h19 |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9464454/ https://www.ncbi.nlm.nih.gov/pubmed/36101840 http://dx.doi.org/10.2147/JAA.S360381 |
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