期刊
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
卷 8, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2020.00495
关键词
miR-221; asthma; airway inflammation; airway remodeling; ASMCs
资金
- National Natural Science Foundation of China [81370132]
- funding project for the development of Nanjing Medical Technology [JQX15008]
- project of medical talents of Jiangsu Province [QNRC2016087]
- National Natural Youth Science Foundation of China [81700035]
- Scientific and Technological Project from the Department of Science and Technology of Nanjing [201723003]
- cooperative research project of Southeast University-Nanjing Medical University [2242018K3DN20]
- project of Nanjing Medical University [2017njmuzd054]
Background Airway remodeling is one of the most important pathological features of chronic asthma. This study aimed to determine whether microRNA-221 (hereafter, miR-221) can affect airway remodeling in a mouse model of ovalbumin (OVA)-induced chronic asthma. Methods Adeno-associated viruses (AAVs) Bearing miR-221 sponges were used to downregulate miR-221 in asthmatic mice. Staining with hematoxylin and eosin (H&E), Masson trichrome, and periodic acid-Schiff reagent was used to assess histological changes. The affected signaling pathway in mouse airway smooth muscle cells (ASMCs) was also identified by gene chip technology. A PI3K/AKT-inhibitor (LY294002) was used to confirm the role of the pathway in ASMCs. Results The inhibition of miR-221 in a murine asthma model was found to reduce airway hyper-responsiveness, mucus metaplasia, airway inflammation, and airway remodeling (p< 0.05). Furthermore, miR-221 was found to regulate collagen deposition in the extracellular matrix (ECM) of ASMCs. Bioinformatics analysis and western blot analysis confirmed that the PI3K-AKT pathway was involved in ECM deposition in ASMCs. Conclusion miR-221 might play a crucial role in the mechanism of remodeling via the PI3K/AKT pathway in chronic asthma and it could be considered as a potential target for developing therapeutic strategies.
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