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Signaling mechanism of extracellular RNA in endothelial cells

Fischer, Silvia; Nishio, Miwako; Peters, Saskia C.; Tschernatsch, Marlene; Walberer, Maureen; Weidemann, Susanne; Heidenreich, Regina; Couraud, Pierre O.; Weksler, Babette B.; Romero, Ignacio A.; Gerriets, Tibo and Preissner, Klaus T. (2009). Signaling mechanism of extracellular RNA in endothelial cells. FASEB Journal, 23(7) pp. 2100–2109.

DOI (Digital Object Identifier) Link: http://dx.doi.org/10.1096/fj.08-121608
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Abstract

Extracellular RNA has been shown to induce vascular endothelial growth factor (VEGF)-dependent hyperpermeability in vivo as well as in vitro. Studies were performed to investigate the mechanism of these effects. For permeability studies primary cultures of porcine brain-derived microvascular endothelial cells (BMECs) and for all other analytical studies the human brain endothelial cell line HCMEC/D3 or human umbilical vein endothelial cells (HUVECs) were used. RNA, but not DNA, initiated signaling events by binding of VEGF to neuropilin-1, followed by VEGF-R2 phosphorylation, activation of phospholipase C (PLC), and intracellular release of Ca(2+). Activation of these pathways by RNA also resulted in the release of von Willebrand Factor from Weibel-Palade bodies. Pretreatment of cells with heparinase totally abrogated the RNA-induced permeability changes, whereas RNA together with VEGF completely restored VEGF-R2-mediated hyperpermeability. Although poly:IC increased the interleukin-6 release via activation of toll-like receptor-3 (TLR-3), permeability changes mediated by poly:IC or RNA remained unchanged after blocking TLR-3 or NF-kB activation. These results indicate that extracellular RNA serves an important cofactor function to engage VEGF for VEGF-R2-dependent signal transduction, reminiscent of the coreceptor mechanism mediated by proteoglycans, which might be of relevance for the mobilization and cellular activities of RNA-binding cytokines in general.

Item Type: Journal Article
Copyright Holders: 2009 The Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Academic Unit/Department: Science > Life, Health and Chemical Sciences
Interdisciplinary Research Centre: Biomedical Research Network (BRN)
Item ID: 15251
Depositing User: Astrid Peterkin
Date Deposited: 17 Mar 2009 09:38
Last Modified: 07 Mar 2014 15:06
URI: http://oro.open.ac.uk/id/eprint/15251
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