Study Title:

1,25-Dihydroxyvitamin D3 targeting VEGF pathway alleviates house dust mite (HDM)-induced airway epithelial barrier dysfunction.

Study Abstract

Background: In our previous studies, we have indentified that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) can alleviate toluene diisocyanate-induced airway epithelial barrier disruption and we also found that vascular endothelial growth factor (VEGF) derived from airway epithelials cells could disrupt epithelial barrier.

Objective: The study aimed to investigate whether 1,25(OH)2D3 can inhibit house dust mite (HDM) induced airway epithelial barrier dysfunction by regulating the VEGF pathway.

Method: The 16HBE and BEAS-2B cells were cultured and treated according to the experiment requirement. Trans Epithelial Electric Resistance (TEER), permeability of epithelial layer, and distribution and expression of junction proteins were used to evaluate the cell layer barrier function, Western Blot was used to evaluate the expression of junction proteins and phosphorylated Akt in the cells, RT-PCR and ELISA were used to evaluate the VEGF gene expression and protein release in the cells. Recombinant VEGF165 was used to determine the role of the VEGF pathway in the epithelial barrier function.

Results: HDM resulted in a decline in TEER and increase of cell permeability, following abnormal distribution and expression of junction proteins (E-Cadherin and zona occludens (ZO)-1), accompanied by a significant upregulation of VEGF and phosphorylated Akt, which were all partly recovered by treatment with either 1,25(OH)2D3 or PI3K inhibitor LY294002. VEGF165-induced barrier dysfunction was accompanied by disruption of the epithelial E-cadherin and β-catenin, pretreatment of 1,25(OH)2D3 and LY294002 markedly attenuated VEGF-induced airway barrier disruption in 16HBE cells.

Conclusion: 1,25(OH)2D3 can alleviate HDM-induced airway epithelial barrier dysfunction by inhibiting PI3K pathway-dependent VEGF release.

Study Information

Cell Immunol. 2017 Feb;312:15-24. doi: 10.1016/j.cellimm.2016.11.004. Epub 2016 Nov 16. PMID: 27884393.

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