November 13, 2007Science s STKE
Dual Regulation of Endothelial Junctional Permeability
Key Points
- To outline a molecular model describing how distinct G protein-coupled receptor signaling cascades coordinately regulate adherens junction integrity and endothelial barrier permeability.
- Synthesized molecular and cellular evidence detailing GPCR-mediated intracellular signaling pathways in endothelial barrier regulation.
- Evaluated the mechanistic actions of thrombin-stimulated PAR(1) and sphingosine-1-phosphate-stimulated S1P(1) receptors in junction disassembly and barrier repair.
- PAR(1) activation by thrombin induces adherens junction breakdown and cytoskeletal remodeling, driving vascular leakage and inflammatory signaling.
- S1P(1) activation by sphingosine-1-phosphate functionally antagonizes PAR(1) activity to promote adherens junction reannealing and restore barrier integrity.
- Signaling downstream of PAR(1) activation induces S1P(1) receptor engagement as an endogenous feedback mechanism essential for endothelial barrier recovery.
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Discussion
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Implication
Review demonstrates opposing actions of thrombin and sphingosine-1-phosphate on endothelial junctional permeability, suggesting novel targets for anti-inflammatory therapies.
Cite This Study
Komarova et al. (2007) studied this question.