VE-cadherin regulates migration inhibitory factor synthesis and release

Area of Science:

• Cell biology
• Molecular biology
• Vascular physiology

Background:

• Vascular endothelial (VE)-cadherin is crucial for endothelial cell-cell adhesion and maintaining vascular integrity.
• VE-cadherin mediates outside-in signaling, influencing vascular physiology, but the exact signals are not fully understood.

Purpose of the Study:

• To elucidate the nature of signals generated by VE-cadherin outside-in signaling.
• To investigate the role of VE-cadherin in regulating cytokine/chemokine expression and its impact on vascular permeability.

Main Methods:

• Human umbilical vein endothelial cells (HUVECs) were treated with VE-cadherin function-blocking antibodies or siRNA.
• Cytokine/chemokine release was analyzed using antibody arrays, ELISA, Western blot, and qRT-PCR.
• Src kinase activation was assessed, and in vivo studies involved mice models to examine lung vascular leak and inflammation.

Main Results:

• Disruption of VE-cadherin adhesion by antibody BV9 induced the release of migration inhibitory factor (MIF).
• VE-cadherin-mediated MIF release resulted from enhanced MIF mRNA expression, driven by Src kinase activation.
• In vivo, neutralizing MIF partially alleviated lung vascular leak induced by VE-cadherin blockade.

Conclusions:

• VE-cadherin regulates the synthesis and release of MIF through Src kinase signaling.
• These findings support the role of VE-cadherin in translating cell-cell adhesion status into intracellular signals that modulate gene expression.