PEDF Regulates Vascular Permeability by a γ-Secretase-Mediated Pathway
2011

PEDF Regulates Vascular Permeability by a γ-Secretase-Mediated Pathway

Sample size: 18 publication Evidence: high

Author Information

Author(s): Cai Jun, Wu Lin, Qi Xiaoping, Li Calzi Sergio, Caballero Sergio, Shaw Lynn, Ruan Qing, Grant Maria B., Boulton Michael E.

Primary Institution: University of Florida

Hypothesis

Does inhibition of VEGF-induced permeability by PEDF involve a γ-secretase-mediated mechanism?

Conclusion

PEDF regulates VEGF-induced vascular permeability via a novel γ-secretase dependent pathway.

Supporting Evidence

  • PEDF significantly reduced VEGF-induced permeability in cultured cells.
  • PEDF's effect was greatest when applied 6 hours after VEGF treatment.
  • γ-secretase inhibition blocked the beneficial effects of PEDF on permeability.
  • Immunohistochemistry showed that PEDF prevented VEGF-induced dissociation of junctional complexes.
  • Intravitreal injection of PEDF inhibited VEGF-induced leakage in mice.

Takeaway

This study shows that a protein called PEDF can help keep blood vessels in the eye from leaking too much, which is important for preventing vision problems in diabetes.

Methodology

Vascular permeability was assessed in vitro by measuring transendothelial resistance and paracellular permeability to dextran, and in vivo by following leakage of intravenous FITC-labelled albumin into the retina.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0021164

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