Glycyrrhizinate attenuates exosome induced endothelial cell proliferation and permeability through p38 pathway

Abstract

Purpose: To investigate the mechanism of action involved in the treatment of severe burn injury with glycyrrhizinate (DG). Methods: Exosomes were purified from sera of patients with burn injury using an ultra-high-speed centrifuge, and verified by western blot. Cell proliferation and permeability were assessed using cell counting kit (CCK)-8, transepithelial-transendothelial electrical resistance (TEER), and Fluorescein Isothiocyanate (FITC) dextran assays, while immunoblotting was used for assay of the levels of p38, occluding, and zonula occludens 1 (ZO-1). Results: Serum-derived exosomes (serum-exo) significantly suppressed cell proliferation while causing hyperpermeability in HUVECs (p < 0.001). Furthermore, DG alleviated the hyperpermeability and inhibition of cell proliferation caused by serum-exo (p < 0.001). In addition, the upregulation of p-P38 induced by serum-exo decreased upon DG treatment. Interestingly, the effect of DG was blocked by anisomycin, a specific p38 activator, indicating that p38 signaling pathway may contribute to the function of DG. Conclusion: Glycyrrhizinate attenuates serum-exo-induced cell proliferation and permeability alteration via p38 signaling pathway, thereby making it a potential agent for the management of severe burn injury.