Suppression of microRNA-384 enhances autophagy of airway smooth muscle cells in asthmatic mouse
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Zhe Cheng1, Xi Wang1, Lingling Dai1, Liuqun Jia1, Xiaogang Jing1, Ying Liu1, Huan Wang1, Pengfei Li1, Lin An1 and Meng Liu1
1Department of Respiratory and Critical Care Medicine, Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
Zhe Cheng, email: [email protected]
Keywords: asthma, ovalbumin (OVA), miR-384, beclin-1, autophagy, airway smooth muscle (ASM) cells
Received: May 01, 2017 Accepted: May 22, 2017 Published: July 01, 2017
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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