Inhibitory Effects of Resveratrol on Airway Remodeling by Transforming Growth Factor-β/Smad Signaling Pathway in Chronic Asthma Model.
Inhibitory Effects of Resveratrol on Airway Remodeling by Transforming Growth Factor-β/Smad Signaling Pathway in Chronic Asthma Model.
复制标题
DOI：
10.4168/aair.2017.9.1.25
复制
发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Lee SY
中科院分区：
文献类型：
--
作者：
Lee HY;Kim IK;Yoon HK;Kwon SS;Rhee CK;Lee SY
哮喘是一种以气道重塑为特征的慢性气道疾病，导致肺功能进行性下降。减轻气道重塑的治疗剂可以补充传统糖皮质激素的有限作用。在这项研究中，我们研究了白藜芦醇对慢性支气管哮喘小鼠模型过敏性气道炎症和重塑的影响。用3个月反复暴露于卵清蛋白（OVA）的小鼠中发生的支气管平滑肌增厚用于研究气道重塑。在OVA攻击期间每天给予口服白藜芦醇。在存在或不存在白藜芦醇的情况下，检测支气管上皮细胞中TGF-β1/Smad信号蛋白和下游间充质标志物的表达。OVA致敏和慢性激发增加气道高反应性、炎症、杯状细胞增生、α-平滑肌肌动蛋白（SMA）和胶原沉积。白藜芦醇能有效抑制OVA诱导的气道炎症和重塑。白藜芦醇可有效抑制OVA攻击小鼠肺组织TGF-β1/磷酸化Smad 2/3的表达。在支气管上皮细胞中，TGF-β1诱导的间充质标志物snail、slug、vimentin和α-SMA的表达被白藜芦醇处理抑制。白藜芦醇有效地改善了支气管哮喘小鼠模型的气道炎症和气道结构变化。这些作用是通过降低TGF-β1表达介导的，进而抑制TGF-β1/Smad信号传导和上皮-间充质转化过程。我们的研究结果表明，白藜芦醇治疗支气管哮喘相关的气道重塑的潜在好处。
Asthma is a chronic airway disease characterized by airway remodeling, leading to a progressive decline in lung function. Therapeutic agents that attenuate airway remodeling can complement the limited effects of traditional glucocorticoids. In this study, we investigated the effect of resveratrol on allergic airway inflammation and remodeling in a murine model of chronic bronchial asthma. Peribronchial smooth muscle thickening that developed in mice challenged with a 3-month repeated exposure to ovalbumin (OVA) was used to study airway remodeling. Oral resveratrol was administered daily during the OVA challenge. The expression of TGF-β1/Smad signaling proteins and downstream mesenchymal markers in the presence or absence of resveratrol was examined in bronchial epithelial cells. OVA sensitization and chronic challenge increased airway hyperresponsiveness, inflammation, goblet cell hyperplasia, α-smooth muscle actin (SMA), and collagen deposition. Resveratrol effectively suppressed OVA-induced airway inflammation and remodeling. The expression of TGF-β1/phosphorylated Smad2/3 was increased in the lung tissues of OVA-challenged mice but effectively inhibited by resveratrol. In bronchial epithelial cells, the TGF-β1-induced expression of the mesenchymal markers snail, slug, vimentin, and α-SMA was suppressed by resveratrol treatment. Resveratrol effectively ameliorated both airway inflammation and airway structural changes in a mouse model of bronchial asthma. These effects were mediated by decreased TGF-β1 expression, in turn suppressing TGF-β1/Smad signaling and the epithelial-mesenchymal transition process. Our results demonstrate the potential benefits of resveratrol for the treatment of airway remodeling associated with bronchial asthma.