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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.

Icariin which is a flavonoid glucoside isolated from Epimedium brevicornu Maxim, has been reported to have anti-osteoporotic, anti-inflammatory and anti-depressant-like activities. In this study, we observed the effect of icariin on airway inflammation of ovalbumin (OVA)-induced murine asthma model and the associated regulatory mode on T-helper (Th)17 and regulatory T (Treg) cell function. Our data revealed that chronic OVA inhalation induced a dramatic increase in airway resistance (RL) and decrease in the lung dynamic compliance (Cdyn), and icariin and DEX treatment caused significant attenuation of such airway hyperresponsiveness (AHR). BALF cell counts demonstrated that icariin and DEX led to a prominent reduction in total leukocyte as well as lymphocyte, eosinophil, neutrophil, basophil and monocyte counts. Histological analysis results indicated that icariin and DEX alleviated the inflammatory cells infiltrating into the peribronchial tissues and goblet cells hyperplasia and mucus hyper-production. Flow cytometry test demonstrated that icariin or DEX administration resulted in a significant percentage reduction in CD4+RORγt+ T cells and elevation of CD4+Foxp3+ T cells in BALF. Furthermore, icariin or DEX caused a significant reduction in IL-6, IL-17 and TGF-β level in BALF. Unfortunately, icariin had no effect on IL-10 level in BALF. Western blot assay found that icariin or DEX suppressed RORγt and promoted Foxp3 expression in the lung tissue. qPCR analysis revealed that icariin and DEX resulted in a notable decrease in RORγt and increase in Foxp3 mRNA expression in isolated spleen CD4+ T cell. In conclusion, our results suggested that icariin was effective in the attenuation of AHR and chronic airway inflammatory changes in OVA-induced murine asthma model, and this effect was associated with regulation of Th17/Treg responses, which indicated that icariin may be used as a potential therapeutic method to treat asthma with Th17/Treg imbalance phenotype. [ABSTRACT FROM AUTHOR]