Pigment Epithelium-Derived Factor Induces Endothelial Barrier Dysfunction via p38/MAPK Phosphorylation

Area of Science:

• Vascular Biology
• Cell Signaling
• Biochemistry

Background:

• Endothelial barrier dysfunction is a critical factor in inflammatory conditions, leading to edema and organ failure.
• Pigment epithelium-derived factor (PEDF) is an endogenous antagonist with diverse biological roles, but its effect on endothelial barrier function is unknown.

Purpose of the Study:

• To investigate the role of PEDF in regulating endothelial barrier integrity.
• To elucidate the signaling pathways involved in PEDF-induced endothelial dysfunction.

Main Methods:

• Utilized human umbilical vein endothelial cells (HUVECs) in vitro.
• Administered exogenous PEDF and measured FITC-dextran leakage and transendothelial electrical resistance (TER).
• Assessed the involvement of p38/MAPK signaling and cytoskeletal changes (microtubules and F-actin).

Main Results:

• Exogenous PEDF dose- and time-dependently activated the p38/MAPK signaling pathway.
• PEDF induced vascular hyperpermeability, evidenced by increased FITC-dextran leakage and decreased TER.
• PEDF treatment led to microtubule disassembly and F-actin rearrangement.
• The p38/MAPK inhibitor SB203580 attenuated PEDF-induced endothelial barrier dysfunction.

Conclusions:

• PEDF acts as a vasoactive substance that promotes vascular hyperpermeability.
• The p38/MAPK pathway is crucial for PEDF-mediated endothelial barrier dysfunction.
• PEDF and p38/MAPK represent potential therapeutic targets for maintaining vascular integrity.