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

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.

Automated summary

Airway epithelial barrier dysfunction is crucial in asthma pathogenesis and leads to enhanced downstream inflammatory signaling. S100 calcium binding protein A4 (S100A4), which promotes metastasis, has been found as an effective inflammatory factor elevated in bronchoalveolar lavage fluid in asthmatic mice. Vascular endothelial growth factor-A (VEGFA) is considered a vital regulator in vascular physiological activities. This study explored the function of S100A4 and VEGFA in an asthma model induced by house dust mite (HDM) extracts. The results demonstrate that secreted S100A4 causes epithelial barrier dysfunction, airway inflammation, and the release of T-helper 2 cytokines through the activation of VEGFA/VEGFR2 signaling pathway, and can be partially reversed by S100A4 polyclonal antibody, niclosamide, and S100A4 knockdown, suggesting a potential therapeutic target for airway epithelial barrier dysfunction in asthma.