Pigment epithelium-derived factor (PEDF) binds to caveolin-1 and inhibits the pro-inflammatory effects of caveolin-1 in endothelial cells.

Abstract

Pigment epithelium-derived factor (PEDF) exerts atheroprotective effects both in cell culture and animal models through its anti-oxidative and anti-inflammatory properties. Caveolin-1 (Cav), a major protein component of caveolae in endothelial cells (ECs), plays a role in the progression of atherosclerosis. However, effects of PEDF on Cav-exposed ECs remain unknown. In this study, we examined whether and how PEDF could inhibit the Cav-induced inflammatory and thrombogenic reactions in human umbilical vein ECs (HUVECs). Surface plasmon resonance revealed that PEDF bound to Cav at the dissociation constant of 7.36×10(-7) M. Further, one of the major Cav-interacting proteins in human serum was identified as PEDF by peptide mass fingerprinting analysis using BIAcore 1000 combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Exogenously added Cav was taken up into the membrane fraction of HUVECs and dose-dependently increased monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1) and plasminogen activator inhibitor-1 (PAI-1) mRNA levels, all of which were blocked by the simultaneous treatment with 10nM PEDF. Small interfering RNAs directed against Cav decreased endogenous Cav levels and suppressed gene expression of MCP-1, VCAM-1 and PAI-1 in HUVECs. This study indicates that PEDF binds to Cav and could block the inflammatory and thrombogenic reactions in Cav-exposed HUVECs. Our present study suggests that atheroprotective effects of PEDF might be partly ascribed to its Cav-interacting properties.

• Authors: Takanori Matsui, Yuichiro Higashimoto, Junichi Taira, Sho-ichi Yamagishi
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 441 Issue 2 Pg. 405-10 (Nov 15 2013) ISSN: 1090-2104 [Electronic] United States
• PMID: 24161393 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• CAV1 protein, human
• CCL2 protein, human
• Caveolin 1
• Chemokine CCL2
• Eye Proteins
• Nerve Growth Factors
• Plasminogen Activator Inhibitor 1
• RNA, Small Interfering
• Serpins
• Vascular Cell Adhesion Molecule-1
• pigment epithelium-derived factor

Topics

• Atherosclerosis (genetics, metabolism)
• Caveolin 1 (genetics, metabolism, pharmacology)
• Chemokine CCL2 (genetics)
• Eye Proteins (genetics, metabolism, pharmacology)
• Gene Expression (drug effects)
• Human Umbilical Vein Endothelial Cells (metabolism)
• Humans
• Inflammation (genetics, metabolism)
• Nerve Growth Factors (genetics, metabolism, pharmacology)
• Plasminogen Activator Inhibitor 1 (genetics)
• RNA, Small Interfering (genetics)
• Serpins (genetics, metabolism, pharmacology)
• Thrombosis (genetics, metabolism)
• Vascular Cell Adhesion Molecule-1 (genetics)