Role of Wnt/β-catenin/VEGF pathway in endothelial cell damage caused by Haemophilus parasuis in pigs
To investigate the changes of vascular endothelial barrier during exudative inflammation caused by Haemophilus parasuis(HPS)in pigs,primary pig vascular endothelial cells were infected with HPS.The effects on the expression of the Wnt/β-catenin pathway and its downstream target genes were de-tected by Western blot and fluorescence quantitative PCR,and the alterations in the structure of intercellu-lar adhesion junctions were detected by indirect immunofluorescence and transendothelial electrical resis-tance assay.The results showed that HPS infection activated Wnt/β-catenin pathway in porcine endothelial cells,and induced nuclear translocation of β-catenin protein in the cytoplasm,resulting in the destruction of the adhesive junction structure composed of β-catenin and VE-cadherin at the cell membrane and the in-crease of cell permeability.Moreover,inhibition of the expression of VEGF gene downstream of Wnt/β-catenin pathway significantly suppressed the nuclear translocation of β-catenin and markedly restored the in-tercellular adherens junctions composed of β-catenin and VE-cadherin,which benefits the recovery of endo-thelial cell permeability.These results suggested that HPS infection disrupted intercellular adherens junc-tions and increased endothelial cell permeability by activating the Wnt/β-catenin pathway in porcine endo-thelial cells;meanwhile,the VEGF gene downstream of the Wnt/β-catenin pathway amplifies the Wnt/β-catenin pathway activity and cell damage induced by HPS infection through a positive feedback.
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