Evidence map›Paper›PMID 21068089›Full record

ArticleAnnals of the rheumatic diseases2011

dsRNA activation of endothelin-1 and markers of vascular activation in endothelial cells and fibroblasts.

Giuseppina Farina, Michael York, Cindy Collins, Robert Lafyatis

Open access · greenAbstract read
In one paragraph

Article in Annals of the rheumatic diseases, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.2field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. CirculatoryGenes · 2021
    Article
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  4. Observational
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  6. Review
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  8. The role of adipokines in systemic sclerosis: a missing link?Archives of dermatological research · 2019
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Giuseppina FarinaBoston University School of Medicine, Arthritis Center, E5, 72 E Concord Street, Boston, MA 02118, USA.
Michael York
Cindy Collins
Robert Lafyatis
Boston University · US

Funding

Innate immunity in dermal fibrosis and systemic sclerosisR01AR051089 · NIAMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LAFYATIS, ROBERT A. · 2005 to 2015
$2.8M
Microarray biomarkers of disease activity and progression in systemic sclerosisU01AR055063 · NIAMS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI LAFYATIS, ROBERT A. · 2007 to 2009
$639k
Interplay between Type I IFN and TGF-beta signaling in systemic sclerosisR03AR062721 · NIAMS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI FARINA, GIUSEPPINA ALESSANDRA · 2012 to 2014
$240k
NIAMS NIH HHS R01 AR051089NIAMS NIH HHS R01AR051089NIAMS NIH HHS R03 AR062721NIAMS NIH HHS U01 AR055063PHS HHS U0IAR055063
6 · The paper itself

Abstract

backgroundIn patients with systemic sclerosis (SSc), the relationship between innate immune activation, represented by increased expression of interferon (IFN)-regulated genes, and vascular injury/activation, manifest by increased endothelin-1 (ET-1), endothelin converting enzyme-1 (ECE1) and intercellular adhesion molecule-1, is uncertain.

objectiveTo investigate the potential roles of innate immune ligands in both these pathogenic pathways.

methodsThe effect of known Toll-like receptor (TLR) ligands was tested in vitro on dermal microvascular and pulmonary arterial endothelial cells, and on dermal fibroblasts cultured from healthy controls and patients with SSc. To test the effect of double-stranded RNA (dsRNA) on vascular activation/injury in vivo, polyinosinic/polycytidylic acid (poly(I:C)) was administered continuously over 7 days by subcutaneous osmotic pump.

resultsdsRNA/poly(I:C), but not other TLR ligands, highly stimulated ET-1 protein and mRNA (EDN1), as well as intercellular adhesion molecule-1 (ICAM-1) and IFN-regulated MX2, by endothelial cells and dermal fibroblasts. Poly(I:C) induced EDN1, ECE1, and ICAM-1 mRNA expression in poly(I:C) treated skin. Poly(I:C)-induced EDN1, ECE1 and MX2 was not blocked in mice with the type I IFN receptor deleted. However, poly(I:C)-induced EDN1 and ECE1, but not poly(I:C)-induced ICAM-1 expression was blocked in mice with the TLR3 signalling protein TRIF/TICAM-1 deleted.

conclusionTogether these data show that the dsRNA can regulate genes associated with vascular activation, as seen in SSc, that type I IFNs do not mediate these effects, and that EDN1 and ECE1 but not ICAM-1 activation is mediated by TLR3.

Indexed as

AnimalsCells, CulturedEndothelial CellsEndothelin-1Endothelium, VascularFibroblastsGene Expression RegulationGTP-Binding ProteinsHumansImmunity, InnateLigandsMiceMice, Inbred C57BLMyxovirus Resistance ProteinsPoly I-CPulmonary ArteryEndothelin-1GTP-Binding ProteinsLigandsMx2 protein, mouseMyxovirus Resistance ProteinsPoly I-CRNA, Double-StrandedRNA, MessengerTLR3 protein, humanToll-Like Receptor 3

Identifiers

PMID21068089
PMCPMC3086552
OpenAlexW2130572501

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.