SPAK-p38 MAPK signal pathway modulates claudin-18 and barrier function of alveolar epithelium after hyperoxic exposure

Abstract Background Hyperoxia downregulates the tight junction (TJ) proteins of alveolar epithelium and leads to barrier dysfunction. Previous study has showed that STE20/SPS1-related proline/alanine-rich kinase (SPAK) interferes with intestinal function in mice. The aim present is explore association between SPAK after hyperoxic exposure. Methods Hyperoxic acute lung injury (HALI) was induced by exposing mice > 99% oxygen for 64 h. were randomly allotted into four groups comprising two control without knockout. Mouse MLE-12 cells cultured conditions or knockdown. Transepithelial electric resistance transwell monolayer permeability measured each group. In-cell western assay used screen possible mechanism p-SPAK being hyperoxia. Results Compared group, knockout had a lower protein level bronchoalveolar lavage fluid HALI, which correlated extent TJ disruption according transmission electron microscopy. down-regulated claudin-18 epithelium, alleviated In cells, hyperoxia up-regulated phosphorylated-SPAK reactive species (ROS), inhibited indomethacin. knockdown higher transepithelial electrical expression suppressed hyperoxia, down-regulation restored claudin-18. process suppressing impairing mediated p38 mitogen-activated (MAPK). Conclusions up-regulates SPAK-p38 MAPK signal pathway ROS, disrupts attenuates this protects against dysfunction