Role of moesin in the effect of glucagon-like peptide-1 on advanced glycation end products-induced endothelial barrier dysfunction

Glucagon-like peptide-1 (GLP-1) analogues have been found to exert protective effect on endothelial barrier dysfunction in vascular diseases. Moesin phosphorylation participates in the process of advanced glycation end products (AGEs) induced disruption of endothelial barrier integrity. Whether and how GLP-1 modulating moesin phosphorylation in endothelium under diabetic condition needs further clarification. Consistent with previous studies, our data showed that hyperglycemia and AGEs promoted moesin phosphorylation in ECs in vivo and vitro experiments. With or without AGEs incubation, overexpression of moesin and activated mutant moesin T558D increased ECs permeability, whereas knockdown of moesin decreased ECs permeability. Inhibition of Rho/ROCK, p38/MAPK and PKC 13 signal pathways also decreased moesin phosphorylation in ECs incubated with AGEs. Importantly, GLP-1 inhibited moesin phosphorylation in AGE-induced ECs in a dose-dependent manner. Intriguingly, the effects of GLP-1 elicited on moesin phosphorylation in ECs under diabetic condition were blunted by inhibition of cAMP/PKA and stimulation of Rho/ROCK, p38 and PKC 13 signaling pathways. Therefore, this study verified that the stabilizing effect of GLP-1 on the moesin phosphorylation mediated endothelial barrier function is mediated by GLP-1R/cAMP/PKA activation and subsequent down-regulation of Rho/ROCK, p38 and PKC 13 signaling pathways.

Automated summary

GLP-1 analogues exert a protective effect on endothelial barrier function in vascular diseases by inhibiting Moesin phosphorylation to maintain endothelial barrier integrity. Under diabetic conditions, the effects of GLP-1 on Moesin phosphorylation in endothelial cells are mediated through GLP-1R/cAMP/PKA activation and subsequent down-regulation of Rho/ROCK, p38, and PKC 13 signaling pathways.