Differential regulation of VE‐cadherin and N‐cadherin levels by p120

Endothelial cells express both VE‐cadherin, which is endothelial specific, and N‐cadherin. Our lab has shown that association of p120 with VE‐cadherin is required for maintaining VE‐cadherin levels and endothelial barrier integrity. We expected that N‐cadherin levels, like VE‐cadherin levels, would be regulated by p120. However, altering the amount of p120 in bovine pulmonary artery endothelial cells (BPAEC) using either adenovirus or siRNA did not affect N‐cadherin levels. We have found that different endothelial cells express widely varying levels of N‐cadherin. Increasing N‐cadherin expression in human lung microvascular endothelial cells, which express little endogenous N‐cadherin, resulted in increased junctional localization of N‐cadherin as opposed to diffuse distribution across the surface of the cell, and also a decrease in VE‐cadherin, which we hypothesized was due to competition for p120. This was confirmed by co‐expressing p120 with N‐cadherin, which prevented the decrease in VE‐cadherin. We also found that high level expression of N‐cadherin in BPAEC resulted in a decrease in barrier function as assessed by changes in electrical resistance and permeability to fluorescent‐labeled albumin suggesting that N‐cadherin‐p120 interactions were not as effective as VE‐cadherin‐p120 interaction at supporting endothelial barrier function. This data illustrates that although p120 associates with both cadherins in endothelial cells, N‐cadherin, unlike VE‐cadherin, is not subject to regulation by p120 and does not promote endothelial barrier function. K02‐HL‐04332; R01‐HL‐68079; T32‐HL‐07194