MicroRNA-182-5p Attenuates Asthmatic Airway Inflammation by Targeting NOX4.
MicroRNA-182-5p Attenuates Asthmatic Airway Inflammation by Targeting NOX4.
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MicroRNA-182-5p 通过靶向 NOX4 减轻哮喘气道炎症
DOI：
10.3389/fimmu.2022.853848
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
哮喘以慢性呼吸道炎症、气道高反应性和气道重塑为特征。MicroRNA(MiRNA)最近被认为与哮喘的发病机制有关。然而，不同的miRNAs在哮喘中的作用机制复杂，miRNA-182-5p在哮喘中的作用机制尚不清楚。在此，我们旨在探讨miRNA182-5P在哮喘相关气道炎症中的作用机制。建立卵白蛋白(OVA)诱导的哮喘模型。应用miRNA微阵列技术分析哮喘模型中差异表达的miRNAs。我们发现，在OVA诱导的哮喘中，miRNA-182-5p的表达显著降低。在体外，IL-13刺激BEAS-2B细胞后，NOX4(烟酰胺腺嘌呤二核苷酸磷酸氧化酶4)的表达显著上调，伴随线粒体损伤诱导的细胞凋亡，NLRP3(NOD样受体家族吡咯环结构域3)/IL-1β活化，miRNA182-5p减少。相反，miRNA182-5p的过表达显著抑制了上皮细胞的凋亡和NLRP3/IL-1β的激活。此外，我们还发现miRNA-182-5p可以结合到NOX4 mRNA的3‘非转录区域，并通过减少氧化应激和线粒体损伤来抑制上皮细胞的炎症。体内实验表明，miRNA-182-5p可显著降低小鼠肺泡灌洗液中嗜酸粒细胞的百分率，下调IL-4、IL-5和OVA诱导的IL-13等Th2型炎症因子的表达。同时，miRNA-182-5p Agomir可减轻大鼠支气管周围炎性细胞的浸润、杯状细胞的增殖和胶原沉积。总之，靶向miRNA-182-5p可能为哮喘的治疗提供一种新的策略。
Bronchial asthma is characterized by chronic airway inflammation, airway hyperresponsiveness, and airway remodeling. MicroRNA (miRNA) has recently been implicated in the pathogenesis of asthma. However, the mechanisms of different miRNAs in asthma are complicated, and the mechanism of miRNA-182-5p in asthma is still unclear. Here, we aim to explore the mechanism of miRNA182-5p in asthma-related airway inflammation. Ovalbumin (OVA)-induced asthma model was established. MiRNA Microarray Analysis was performed to analyze the differentially expressed miRNAs in the asthma model. We found that the expression of miRNA-182-5p was significantly decreased in OVA-induced asthma. In vitro, IL-13 stimulation of BEAS-2B cells resulted in a significant up-regulation of NOX4 (nicotinamide adenine dinucleotide phosphate oxidase 4), accompanied by mitochondrial damage-induced apoptosis, NLRP3 (NOD-like receptor family pyrin domain-containing 3)/IL-1β activation, and reduced miRNA-182-5p. In contrast, overexpression of miRNA-182-5p significantly inhibited epithelial cell apoptosis and NLRP3/IL-1β activation. In addition, we found that miRNA-182-5p could bind to the 3’ untranscripted region of NOX4 mRNA and inhibit epithelial cell inflammation by reducing oxidative stress and mitochondrial damage. In vivo, miRNA-182-5p agomir treatment significantly reduced the percentage of eosinophils in bronchoalveolar lavage fluid, and down-regulated Th2 inflammatory factors, including IL-4, IL-5, and OVA induced IL-13. Meanwhile, miRNA-182-5p agomir reduced the peribronchial inflammatory cell infiltration, goblet cell proliferation and collagen deposition. In summary, targeting miRNA-182-5p may provide a new strategy for the treatment of asthma.
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DOI：
10.1152/ajplung.00232.2019
发表时间：
2019-09-01
影响因子：
4.9
作者：
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发表时间：
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影响因子：
3.1
作者：
Guo X;Fan Y;Cui J;Hao B;Zhu L;Sun X;He J;Yang J;Dong J;Wang Y;Liu X;Chen J
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影响因子：
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