Ceapin-A7 counteracts the protective effects of Lanreotide in endothelial cells

Background: Pulmonary endothelial barrier dysfunction is characterized by increased vascular permeability, lung edema, and impaired gas exchange. Synthetic somatostatin analogs (SSA), including Lanreotide (LAN), have demonstrated cytoprotective effects in experimental models of endothelial injury, but the corresponding mechanisms mediating those effects are still unclear. Objective: This study aimed to determine whether the unfolded protein response (UPR) sensor ATF6 is involved in the protective outcomes of LAN in lung endothelial cells. Methods: Human and bovine pulmonary endothelial cells were exposed to Ceapin-A7, an ATF6 inhibitor, prior to LAN exposure. Protein expression levels of BiP, Grp94, MLC2, Cofilin, STAT1, STAT3, and stress kinases were assessed. Reactive oxygen species (ROS) generation was also measured, as well as paracellular permeability using FITC-Dextran assay. Results: LAN enhanced protein expression of BiP and Grp94, decreased ROS production, suppressed STAT1, STAT3 and ERK1/2 phosphorylation, and improved barrier function. Those effects were counteracted by Ceapin-A7. Conclusions: Our findings suggest that ATF6 inhibition opposes the beneficial effects of LAN in endothelial cells.