Plakoglobin does not participate in endothelial barrier stabilization mediated by cAMP

Area of Science:

• Endothelial biology
• Cellular signaling
• Vascular permeability

Background:

• Endothelial barrier integrity is crucial for vascular health, regulated by actin cytoskeleton remodeling and cell-junctional proteins.
• Plakoglobin (PG) is a key protein in cell adhesion and signaling, influencing vascular permeability alongside molecules like cAMP and Rho GTPases.

Purpose of the Study:

• To investigate the role of Plakoglobin (PG) in cAMP-mediated stabilization of the endothelial barrier.
• To compare endothelial barrier function in wild-type (WT) and PG knock-out (PG-KO) myocardial endothelial cells.

Main Methods:

• Establishment of myocardial endothelial cells from WT and PG-KO mice.
• Measurement of endothelial barrier function using Transendothelial Electrical Resistance (TEER).
• Analysis of junctional protein expression (VE-cadherin, β-catenin, PECAM-1), phosphatase activity (VE-PTP), and Rho GTPase activity (Rac1, RhoA).

Main Results:

• PG-KO cells exhibited increased basal barrier function with enhanced VE-cadherin and β-catenin at junctions.
• PG deficiency reduced basal intracellular cAMP levels but did not alter VE-cadherin/β-catenin complex composition or Rac1/RhoA activity.
• cAMP augmentation improved barrier function and Rac1 activity in both cell types, though less effectively in PG-KO cells.

Conclusions:

• Plakoglobin plays a role in regulating basal endothelial barrier function and modulates the response to cAMP-mediated barrier stabilization.
• The absence of PG leads to an intrinsically tighter endothelial barrier, but impairs the cell's ability to further strengthen in response to cAMP.