Effect of moesin phosphorylation on high‑dose sphingosine‑1‑phosphate‑induced endothelial responses.

It was previously reported that low-dose sphingosine-1-phosphate (S1P) enhanced endothelial barrier integrity, whereas high-dose S1P induced endothelial monolayer hyperpermeability responses. A number of studies have revealed the underlying molecular mechanisms of the physiological-dose of S1P on barrier-protective effect. However, little work has been performed to determine the effect of S1P-induced endothelial barrier responses. In the present study, the role of moesin phosphorylation in excessive S1P-induced endothelial hyperpermeability was investigated by western blotting, fluorescence staining and transendothelial electrical resistance detection. It was revealed that S1P induced moesin phosphorylation in a time- and concentration-dependent manner. In addition, it was confirmed that high-dose S1P-induced moesin phosphorylation occurred via S1P receptor 2 (S1PR2). Moesin phosphorylation was required for S1P-induced F-actin rearrangement and endothelial barrier disruption. The results suggested that the S1PR2-moesin axis is involved in high-dose S1P-induced endothelial barrier responses. The results of the present study may provide novel therapeutic targets for endothelial injury-associated vascular disorders.