Secreted S100A4 causes asthmatic airway epithelial barrier dysfunction induced by house dust mite extracts via activating VEGFA/VEGFR2 pathway

• Published in: Environmental toxicology Vol. 38; no. 6; pp. 1431 - 1444
• Main Authors: Huang, Chaowen, Zheng, Dongyan, Fu, Chunlai, Cai, Ziwei, Zhang, He, Xie, Zhefan, Luo, Lishan, Li, Huifang, Huang, Yanming, Chen, Jialong
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.06.2023; Wiley Subscription Services, Inc
• Subjects: Animals; Antibodies; Asthma; Asthma - chemically induced; Atmospheric particulates; Bronchus; Calcium; Calcium signalling; Calcium-binding protein; Cytokines; Dermatophagoides pteronyssinus; Disease Models, Animal; Dust; dust mites; ecotoxicology; epithelial barrier; epithelium; Growth factors; House dust; house dust mite; Inflammation; Lavage; Metastases; metastasis; Mice; Mites; Niclosamide; Pathogenesis; Physiological effects; Polyclonal antibodies; Pyroglyphidae; Respiratory tract; Respiratory tract diseases; S100A4; S100A4 protein; Signal transduction; Therapeutic targets; therapeutics; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A; VEGFA/VEGFR2 pathway; S100A4; asthma; epithelial barrier; house dust mite; VEGFA/VEGFR2 pathway
• ISSN: 1520-4081; 1522-7278; 1522-7278
• DOI: 10.1002/tox.23776

The airway epithelial barrier dysfunction plays a crucial role in pathogenesis of asthma and causes the amplification of downstream inflammatory signal pathway. S100 calcium binding protein A4 (S100A4), which promotes metastasis, have recently been discovered as an effective inflammatory factor and elevated in bronchoalveolar lavage fluid in asthmatic mice. Vascular endothelial growth factor‐A (VEGFA), is considered as vital regulator in vascular physiological activities. Here, we explored the probably function of S100A4 and VEGFA in asthma model dealt with house dust mite (HDM) extracts. Our results showed that secreted S100A4 caused epithelial barrier dysfunction, airway inflammation and the release of T‐helper 2 cytokines through the activation of VEGFA/VEGFR2 signaling pathway, which could be partial reversed by S100A4 polyclonal antibody, niclosamide and S100A4 knockdown, representing a potential therapeutic target for airway epithelial barrier dysfunction in asthma.