Department of Laboratory Medicine, The First Affiliated Hospital of Zhengzhou University, Key Clinical Laboratory of Henan Province, Zhengzhou, He'nan 450052, PR China.
Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, He'nan 450052, PR China; Henan Key Laboratory for Pharmacology of Liver Diseases, Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, He'nan 450052, PR China.
Int Immunopharmacol. 2021 Aug;97:107690. doi: 10.1016/j.intimp.2021.107690. Epub 2021 Apr 30.
It has recently been shown that expression levels of tissue factor (TF) are high in the serum and peripheral blood mononuclear cells of patients with asthma. However, whether TF impacts airway inflammation and remodelling in asthma remains unknown. The aim of this study was to investigate the effect of TF in asthma airway inflammation and remodelling using a house dust mite (HDM)-induced chronic asthma model and human bronchial epithelial (16HBE) cells. A chronic asthma model was constructed in BALB/c mice by the intranasal instillation of HDM. Mice were treated with short hairpin TF (shTF), and airway inflammation and remodelling features of asthma and epithelial-mesenchymal transition (EMT) were assessed. 16HBE cells were induced by transforming growth factor-β1 (TGF-β1) and HDM in the presence or absence of shTF; then, EMT markers and invasion and migration ability were determined. TF expression increased in the lung tissue and 16HBE cells when exposed to HDM. TF downregulation in the lung significantly reduced airway hyperresponsiveness, eosinophil inflammation, the EMT process, and levels of interleukin (IL)-4, IL-6, IL-13, and TGF-β1 in bronchoalveolar lavage fluid of asthmatic mice. Moreover, TF downregulation inhibited migration and incursion and decreased the expression levels of fibronectin 1 and TGF-β1, but increased the expression of E-cadherin in HDM- and TGF-β1-stimulated 16HBE cells. These results demonstrated that TF promoted airway pathological features by enhancing the EMT of bronchial epithelial cells both in vitro and in mice with house dust mite-induced asthma.
最近的研究表明，哮喘患者的血清和外周血单个核细胞中组织因子（TF）的表达水平较高。然而，TF 是否影响哮喘的气道炎症和重塑尚不清楚。本研究旨在通过屋尘螨（HDM）诱导的慢性哮喘模型和人支气管上皮（16HBE）细胞，研究 TF 在哮喘气道炎症和重塑中的作用。通过鼻腔内滴注 HDM 构建 BALB/c 小鼠慢性哮喘模型。用短发夹 TF（shTF）处理小鼠，评估哮喘气道炎症和重塑特征以及上皮-间充质转化（EMT）。在存在或不存在 shTF 的情况下，用转化生长因子-β1（TGF-β1）和 HDM 诱导 16HBE 细胞，然后测定 EMT 标志物和侵袭及迁移能力。当暴露于 HDM 时，TF 在肺组织和 16HBE 细胞中的表达增加。肺组织中 TF 的下调显著降低了哮喘小鼠的气道高反应性、嗜酸性粒细胞炎症、EMT 过程以及支气管肺泡灌洗液中白细胞介素（IL）-4、IL-6、IL-13 和 TGF-β1 的水平。此外，TF 的下调抑制了迁移和侵袭，并降低了纤维连接蛋白 1 和 TGF-β1 的表达水平，但增加了 HDM 和 TGF-β1 刺激的 16HBE 细胞中 E-钙黏蛋白的表达。这些结果表明，TF 通过增强支气管上皮细胞的 EMT，在体外和屋尘螨诱导的哮喘小鼠中促进气道病理特征。
