Tissue factor promotes airway pathological features through epithelial-mesenchymal transition of bronchial epithelial cells in mice with house dust mite-induced asthma

被引:10
作者
Zhao, Junwei [1 ]
Jiang, Tianci [2 ,3 ]
Li, Pengfei [2 ,3 ]
Dai, Lingling [2 ]
Shi, Guang [1 ]
Jing, Xiaogang [2 ]
Gao, Shuhui [1 ]
Jia, Liuqun [2 ]
Wu, Shujun [2 ]
Wang, Yu [2 ]
Peng, Youmei [3 ]
Cheng, Zhe [2 ,3 ]
机构
[1] Zhengzhou Univ, Affiliated Hosp 1, Key Clin Lab Henan Prov, Dept Lab Med, Zhengzhou 450052, Henan, Peoples R China
[2] Zhengzhou Univ, Affiliated Hosp 1, Dept Pulm & Crit Care Med, Zhengzhou 450052, Henan, Peoples R China
[3] Zhengzhou Univ, Inst Med & Pharmaceut Sci, Henan Key Lab Pharmacol Liver Dis, Zhengzhou 450052, Henan, Peoples R China
基金
中国国家自然科学基金;
关键词
Asthma; Tissue factor; Airway inflammation; Airway remodelling; Epithelial-mesenchymal transition; GROWTH-FACTOR PRODUCTION; FACTOR RECEPTOR; FACTOR-BETA; TGF-BETA; EXPRESSION; COAGULATION; THROMBIN; PROLIFERATION; INFLAMMATION; HEMOSTASIS;
D O I
10.1016/j.intimp.2021.107690
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-I31 (TGF-I31) 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-I31 in bronchoalveolar lavage fluid of asthmatic mice. Moreover, TF downregulation inhibited migration and incursion and decreased the expression levels of fibronectin 1 and TGF-I31, but increased the expression of E-cadherin in HDM- and TGFI31-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.
引用
收藏
页数:10
相关论文
共 57 条
[1]   The alveolar epithelium can initiate the extrinsic coagulation cascade through expression of tissue factor [J].
Bastarache, Julie A. ;
Wang, Ling ;
Geiser, Thomas ;
Wang, Zhengming ;
Albertine, Kurt H. ;
Matthay, Michael A. ;
Ware, Lorraine B. .
THORAX, 2007, 62 (07) :608-616
[2]   Alternatively spliced human tissue factor: a circulating, soluble, thrombogenic protein [J].
Bogdanov, VY ;
Balasubramanian, V ;
Hathcock, J ;
Vele, O ;
Lieb, M ;
Nemerson, Y .
NATURE MEDICINE, 2003, 9 (04) :458-462
[3]   Asthma - From bronchoconstriction to airways inflammation and remodeling [J].
Bousquet, J ;
Jeffery, PK ;
Busse, WW ;
Johnson, M ;
Vignola, AM .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2000, 161 (05) :1720-1745
[4]   Coagulation factors in the airways in moderate and severe asthma and the effect of inhaled steroids [J].
Brims, F. J. H. ;
Chauhan, A. J. ;
Higgins, B. ;
Shute, J. K. .
THORAX, 2009, 64 (12) :1037-1043
[5]   Epithelial-mesenchymal transition in primary human bronchial epithelial cells is Smad-dependent and enhanced by fibronectin and TNF-alpha [J].
Camara, Joana ;
Jarai, Gabor .
FIBROGENESIS & TISSUE REPAIR, 2010, 3
[6]   Tissue factor- and factor X-dependent activation of protease-activated receptor 2 by factor VIIa [J].
Camerer, E ;
Huang, W ;
Coughlin, SR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (10) :5255-5260
[7]   Airway remodeling-associated mediators in moderate to severe asthma:: Effect of steroids on TGF-β, IL-11, IL-17, and type I and type III collagen expression [J].
Chakir, J ;
Shannon, J ;
Molet, S ;
Fukakusa, M ;
Elias, J ;
Laviolette, M ;
Boulet, LP ;
Hamid, Q .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2003, 111 (06) :1293-1298
[8]  
Cheng Z, 2017, ONCOTARGET, V8, P67933, DOI 10.18632/oncotarget.18913
[9]   Inhibition of airway remodeling in IL-5-deficient mice [J].
Cho, JY ;
Miller, M ;
Baek, KJ ;
Han, JW ;
Nayar, J ;
Lee, SY ;
McElwain, K ;
McElwain, S ;
Friedman, S ;
Broide, DH .
JOURNAL OF CLINICAL INVESTIGATION, 2004, 113 (04) :551-560
[10]   Tissue factor mediates inflammation [J].
Chu, AJ .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2005, 440 (02) :123-132