Role of Intercellular Junctions in Redistribution of Focal Adhesions and Orientation of Vascular Endothelial Cells Exposed to Cyclic Stretching

Abstract

The redistribution of focal adhesions (FAs) containing integrin β1 and paxillin plays an important role in the cyclic stretching-induced morphological changes of endothelial cells (ECs). In addition to focal adhesion kinase (FAK), known to be a primary regulator for FA redistribution, intercellular junctions (IJs) have recently been reported to be involved in signaling upstream of FAs. Here, we addressed the role of IJs in the morphological changes and redistribution of FAs in ECs exposed to cyclic stretching. Both confluent and sparse ECs were oriented nearly perpendicularly to the stretch direction after 10 min of exposure. Orientation of sparse ECs, but not confluent ECs, was suppressed by treatment with a phospho-FAK inhibitor. FAK inhibitor blocked integrin β1 redistribution in ECs, which was observed in non-inhibited cells after 10-min stretch exposure. However, paxillin redistribution in confluent ECs was observed regardless of FAK inhibitor treatment after 2-min stretch exposure. When we blocked signals from IJs with an inhibitor of Src homology 2 domain-containing tyrosine phosphatase-2, the percentage of oriented ECs decreased and paxillin redistribution, but not integrin β1, was suppressed. These findings suggest that IJs are involved in the orientation of ECs subjected to cyclic stretching through signaling pathways other than FAK.