Beta-arrestin-1 mediating protective effects of penehyclidine hydrochloride on changes of F-actin in lipopolysaccharide-stimulated human pulmonary microvascular endothelial cells

In acute lung injury (ALI) and sepsis, the integrity of the endothelial barrier, maintained by endothelial cytoskeleton of microvascular endothelial cells, is important to maintain normal microvascular function. In response to lipopolysaccharide (LPS), F-actin (fibrous actin, F-actin), an essential component of the endothelial cytoskeleton, has been shown to be critical to maintaining the endothelial integrity. Herein, penehyclidine hydrochloride (PHC), an anticholinergic agent manufactured in China, was verified to inhibit p38 MAPK activation, reduce Hsp27 expression, and inhibit LPS-stimulated reorganization of F-actin and formation of stress fiber in this study. Besides, these roles of PHC in human pulmonary microvascular endothelial cells (HPMVEC) were found to be accompanied with its upregulation of beta-arrestin-1. Furthermore, the silencing of beta-arrestin-1 with a shRNA-containing plasmid resulted in an antagonistic effect vs. PHC on the endothelial F-actin function of HPMVEC. In summary, beta-arrestin-1 plays an important role in mediating protective effect of PHC on changes of F-actin in LPS-stimulated HPMVEC.