SEARCH:   Advanced

Blood, 15 February 2007, Vol. 109, No. 4, pp. 1515-1523. Prepublished online as a Blood First Edition Paper on October 5, 2006; DOI 10.1182/blood-2006-07-034009. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-07-034009v1 109/4/1515    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Song, L. Articles by Pachter, J. S. Search for Related Content PubMed PubMed Citation Articles by Song, L. Articles by Pachter, J. S. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Caveolin-1 regulates expression of junction-associated proteins in brain microvascular endothelial cells Li Song1, Shujun Ge1, and Joel S. Pachter1 1 Blood-Brain Barrier Laboratory, Department of Pharmacology, University of Connecticut Health Center, Farmington Recent evidence from this laboratory indicated that reduced expression of caveolin-1 accompanied the diminished expression of tight junction (TJ)–associated proteins occludin and zonula occludens-1 (ZO-1) following stimulation of brain microvascular endothelial cells (BMECs) with the chemokine CCL2 (formerly called MCP-1). Because attenuated caveolin-1 levels have also been correlated with heightened permeability of other endothelia, the objective of this study was to test the hypothesis that reduced caveolin-1 expression is causally linked to the action of CCL2 on BMEC junctional protein expression and barrier integrity. This was achieved using adenovirus to nondestructively deliver caveolin-1 siRNA (Ad-siCav-1) to BMEC monolayers, which model the blood-brain barrier (BBB). Treatment with siRNA reduced the caveolin-1 protein level as well as occludin and ZO-1. Additionally, occludin exhibited dissociation from the cytoskeletal framework. These changes were attended by comparable alterations in adherens junction (AJ)–associated proteins, VE-cadherin and ß-catenin, increased BMEC paracellular permeability, and facilitated the ability of CCL2 to stimulate monocytic transendothelial migration. Furthermore, treating BMECs with cavtratin, a synthetic cell-permeable peptide encoding the caveolin-1 scaffolding domain, antagonized effects of both Ad-siCav-1 and CCL2. These results collectively highlight caveolin-1 loss as a critical step in CCL2-induced modulation of BMEC junctional protein expression and integrity, and possibly serve a crucial role in regulating inflammation at the BBB. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. M. Stamatovic, R. F. Keep, M. M. Wang, I. Jankovic, and A. V. Andjelkovic Caveolae-mediated Internalization of Occludin and Claudin-5 during CCL2-induced Tight Junction Remodeling in Brain Endothelial Cells J. Biol. Chem., July 10, 2009; 284(28): 19053 - 19066. [Abstract] [Full Text] [PDF] A. T. Argaw, B. T. Gurfein, Y. Zhang, A. Zameer, and G. R. John VEGF-mediated disruption of endothelial CLN-5 promotes blood-brain barrier breakdown PNAS, February 10, 2009; 106(6): 1977 - 1982. [Abstract] [Full Text] [PDF] L. Gotloib HISTOLOGY IN EXPERIMENTAL PERITONEAL DIALYSIS: THE LINK BETWEEN STRUCTURE AND FUNCTION Perit. Dial. Int., February 1, 2009; 29(Supplement_2): S36 - S39. [Full Text] [PDF]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020