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.