Evidence map›Paper›PMID 23799952›Full record

ArticleLiver international : official journal of the International Association for the Study of the Liver2013

The CD47-binding peptide of thrombospondin-1 induces defenestration of liver sinusoidal endothelial cells.

Lakshmi Venkatraman, Lisa Tucker-Kellogg

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in Liver international : official journal of the International Association for the Study of the Liver, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
0.7field-weighted citation impact, top 29% 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

32 citing papers in PubMed, 44 citations in OpenAlex.

  1. Actin cytoskeletal dynamics in hepatic myofibroblasts and fibrosis.Nature reviews. Gastroenterology & hepatology · 2026
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4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

2 authors at 2 institutions in 2 countries.

Lakshmi VenkatramanMechanobiology Institute, National University of Singapore, Singapore.
Lisa Tucker-Kellogg
National University of Singapore · SGState University of New York · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsA fenestrated phenotype is characteristic of liver sinusoidal endothelial cells (LSECs), but liver sinusoids become defenestrated during fibrosis and other liver diseases. Thrombospondin-1 (TSP1) is a matrix glycoprotein with pro-fibrotic effects, and the CD47-binding fragment of TSP1 also has anti-angiogenic effects in endothelial cells. We hypothesized that the CD47-binding fragment of TSP1 could induce defenestration in LSECs through the Rho-Rho kinase (ROCK)-myosin pathway.

methodsFreshly isolated rat LSECs were treated with TSP1 or CD47-binding peptides of TSP1. LSEC fenestration was assessed with scanning electron microscopy, and myosin phosphorylation was assessed with immuno-fluorescence.

resultsTreating LSECs with TSP1 caused a dose-dependent loss of fenestrae, and this effect could not be blocked by SB-431542, the TGF-β1 receptor inhibitor. A CD47-binding fragment of TSP1, p4N1, was able to induce defenestration, and a CD47-blocking antibody, B6H12, was able to suppress p4N1-induced defenestration. The p4N1 fragment also caused contraction of fenestra size, correlated with an increase in myosin activation. Pretreatment with Y-237642 (a ROCK inhibitor) prevented p4N1-induced myosin activation and fenestrae decrease. Simvastatin has also been shown to antagonize Rho-ROCK signalling, and we found that simvastatin pretreatment protected LSECs from p4N1-induced myosin activation and defenestration.

conclusionsWe conclude that CD47 signals through the Rho-ROCK-myosin pathway to induce defenestration in LSECs. In addition, our results show that simvastatin and Y-237642 have a beneficial impact on fenestration in vitro, providing an additional explanation for the efficacy of these compounds for regression of liver fibrosis.

Indexed as

Amino Acid SequenceAnalysis of VarianceAnimalsCD47 AntigenEndothelial CellsFluorescent Antibody TechniqueImage Processing, Computer-AssistedLiverMicroscopy, Electron, ScanningMolecular Sequence DataMyosinsPhosphorylationRatsrho-Associated KinasesSignal TransductionCD47 AntigenMyosinsrho-Associated Kinasescapillarizationdiscontinuous endotheliummechanical signal transductionmyosin light chain

Identifiers

PMID23799952
PMCPMC4285809
OpenAlexW2038875372

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.