Advanced glycation end products induce endothelial hyperpermeability via β-catenin phosphorylation and subsequent up-regulation of ADAM10.

ABSTRACT: Endothelial hyperpermeability is the initial event in the development of diabetic microvascular complications, and advanced glycation end products (AGEs) are suggested to cause much of the endothelial hyperpermeability associated with diabetes mellitus, but the molecular mechanism remains to be characterized. β-catenin reportedly plays dual functions in maintaining normal endothelial permeability by serving both as an adhesive component and a signal transduction component. Here, we found that AGEs induced the phosphorylation of β-catenin at residues Y654 and Y142 and the endothelial hyperpermeability was reversed when the two residues were blocked. In mechanism, phosphorylation of Y654 was blocked by Src inactivation, whereas phosphorylation of Y142 was reduced by a focal adhesion kinase i

SUBMITTER: Weng J 

PROVIDER: S-EPMC8358892 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature