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MicroRNA-221 Modulates Airway Remodeling via the PI3K/AKT Pathway in OVA-Induced Chronic Murine Asthma
- Source :
- Frontiers in Cell and Developmental Biology, Vol 8 (2020)
- Publication Year :
- 2020
- Publisher :
- Frontiers Media S.A., 2020.
-
Abstract
- BackgroundAirway 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.MethodsAdeno-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.ResultsThe 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.ConclusionmiR-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.
Details
- Language :
- English
- ISSN :
- 2296634X
- Volume :
- 8
- Database :
- Directory of Open Access Journals
- Journal :
- Frontiers in Cell and Developmental Biology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.7984e849ed944d6b9495b3108d4d10fd
- Document Type :
- article
- Full Text :
- https://doi.org/10.3389/fcell.2020.00495