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Suppression of microRNA-384 enhances autophagy of airway smooth muscle cells in asthmatic mouse

Injury to airway smooth muscle (ASM) cells hallmarks the pathological progression of asthma, a chronic inflammatory airway disease. MicroRNAs (miRNAs) play essential roles in the development of asthma as well as airway remodeling. Here we studied the involvement of miRNAs in the regulation of autoph...

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Autores principales: Cheng, Zhe, Wang, Xi, Dai, Lingling, Jia, Liuqun, Jing, Xiaogang, Liu, Ying, Wang, Huan, Li, Pengfei, An, Lin, Liu, Meng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620225/
https://www.ncbi.nlm.nih.gov/pubmed/28978085
http://dx.doi.org/10.18632/oncotarget.18913
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author Cheng, Zhe
Wang, Xi
Dai, Lingling
Jia, Liuqun
Jing, Xiaogang
Liu, Ying
Wang, Huan
Li, Pengfei
An, Lin
Liu, Meng
author_facet Cheng, Zhe
Wang, Xi
Dai, Lingling
Jia, Liuqun
Jing, Xiaogang
Liu, Ying
Wang, Huan
Li, Pengfei
An, Lin
Liu, Meng
author_sort Cheng, Zhe
collection PubMed
description Injury to airway smooth muscle (ASM) cells hallmarks the pathological progression of asthma, a chronic inflammatory airway disease. MicroRNAs (miRNAs) play essential roles in the development of asthma as well as airway remodeling. Here we studied the involvement of miRNAs in the regulation of autophagic survival of ASM cells and airway disorder. We analyzed autophagy-associated factors LC3 and Beclin-1 by RT-qPCR and protein blotting in purified airway smooth muscle cells from ovalbumin (OVA)-induced asthmatic mice. The biological activity of miRNA targeting Beclin-1 was explored by bioinformatics method and confirmed in a dual luciferase reporter assay. Loss of function experiment was performed via transplantation of miRNA in OVA-induced asthmatic mice. We detected high autophagy levels in ASM cells, which appeared to result from augmentation of Beclin-1 protein, rather than Beclin-1 mRNA, suggesting presence of post-transcriptional control of Beclin-1. Next, miR-384 was figured out to be a Belcin-1-targeting miRNA, which significantly decreased after OVA treatment. Mechanistically, binding of miR-384 to 3’-UTR of Beclin-1 mRNA potently suppressed Beclin-1 protein translation in ASM cells, similar to previous finding in another cell type. In vivo, transplantation of miR-384 significantly attenuated Belcin-1 protein levels in ASM cells, resulting in reduced autophagy of ASM cells and attenuation of asthmatic features by OVA. Together, these data suggest that re-expression of miR-384 may reduce augmentation of Beclin-1-dependent autophagy of ASM cells, as a novel promising treatment for asthma.
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spelling pubmed-56202252017-10-03 Suppression of microRNA-384 enhances autophagy of airway smooth muscle cells in asthmatic mouse Cheng, Zhe Wang, Xi Dai, Lingling Jia, Liuqun Jing, Xiaogang Liu, Ying Wang, Huan Li, Pengfei An, Lin Liu, Meng Oncotarget Research Paper Injury to airway smooth muscle (ASM) cells hallmarks the pathological progression of asthma, a chronic inflammatory airway disease. MicroRNAs (miRNAs) play essential roles in the development of asthma as well as airway remodeling. Here we studied the involvement of miRNAs in the regulation of autophagic survival of ASM cells and airway disorder. We analyzed autophagy-associated factors LC3 and Beclin-1 by RT-qPCR and protein blotting in purified airway smooth muscle cells from ovalbumin (OVA)-induced asthmatic mice. The biological activity of miRNA targeting Beclin-1 was explored by bioinformatics method and confirmed in a dual luciferase reporter assay. Loss of function experiment was performed via transplantation of miRNA in OVA-induced asthmatic mice. We detected high autophagy levels in ASM cells, which appeared to result from augmentation of Beclin-1 protein, rather than Beclin-1 mRNA, suggesting presence of post-transcriptional control of Beclin-1. Next, miR-384 was figured out to be a Belcin-1-targeting miRNA, which significantly decreased after OVA treatment. Mechanistically, binding of miR-384 to 3’-UTR of Beclin-1 mRNA potently suppressed Beclin-1 protein translation in ASM cells, similar to previous finding in another cell type. In vivo, transplantation of miR-384 significantly attenuated Belcin-1 protein levels in ASM cells, resulting in reduced autophagy of ASM cells and attenuation of asthmatic features by OVA. Together, these data suggest that re-expression of miR-384 may reduce augmentation of Beclin-1-dependent autophagy of ASM cells, as a novel promising treatment for asthma. Impact Journals LLC 2017-07-01 /pmc/articles/PMC5620225/ /pubmed/28978085 http://dx.doi.org/10.18632/oncotarget.18913 Text en Copyright: © 2017 Cheng et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Cheng, Zhe
Wang, Xi
Dai, Lingling
Jia, Liuqun
Jing, Xiaogang
Liu, Ying
Wang, Huan
Li, Pengfei
An, Lin
Liu, Meng
Suppression of microRNA-384 enhances autophagy of airway smooth muscle cells in asthmatic mouse
title Suppression of microRNA-384 enhances autophagy of airway smooth muscle cells in asthmatic mouse
title_full Suppression of microRNA-384 enhances autophagy of airway smooth muscle cells in asthmatic mouse
title_fullStr Suppression of microRNA-384 enhances autophagy of airway smooth muscle cells in asthmatic mouse
title_full_unstemmed Suppression of microRNA-384 enhances autophagy of airway smooth muscle cells in asthmatic mouse
title_short Suppression of microRNA-384 enhances autophagy of airway smooth muscle cells in asthmatic mouse
title_sort suppression of microrna-384 enhances autophagy of airway smooth muscle cells in asthmatic mouse
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620225/
https://www.ncbi.nlm.nih.gov/pubmed/28978085
http://dx.doi.org/10.18632/oncotarget.18913
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