Evidence map›Paper›PMID 27159116›Full record

ArticleCell adhesion & migration2017

Wnt5A/Ryk signaling critically affects barrier function in human vascular endothelial cells.

Tom Skaria, Esther Bachli, Gabriele Schoedon

Open access · goldAbstract read
In one paragraph

Article in Cell adhesion & migration, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

33 citing papers in PubMed, 48 citations in OpenAlex.

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  15. WNT/RYK signaling functions as an antiinflammatory modulator in the lung mesenchyme.Proceedings of the National Academy of Sciences of the United States of America · 2022
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  20. Macrophage-derived Wnt signaling increases endothelial permeability during skeletal muscle injury.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2020
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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

3 authors at 2 institutions in 1 country.

Tom Skariaa Inflammation Research Unit, Division of Internal Medicine, University Hospital Zürich , Zürich , Switzerland.
Esther Bachlib Department of Medicine , Uster Hospital , Uster , Switzerland.
Gabriele Schoedona Inflammation Research Unit, Division of Internal Medicine, University Hospital Zürich , Zürich , Switzerland.
University Hospital of Zurich · CHSpital Uster · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Satisfactory therapeutic strategies for septic shock are still missing. Previously we found elevated levels of Wnt5A in patients with severe sepsis and septic shock. Wnt5A is released by activated macrophages but knowledge of its effects in the vascular system remains scant. Here we investigate the response of human coronary artery endothelial cells (HCAEC) to Wnt5A. We used a genome-wide differential expression approach to define novel targets regulated by Wnt5A. Gene ontology analysis of expression profiles revealed clusters of genes involved in actin cytoskeleton remodeling as the predominant targets of Wnt5A. Wnt5A targeted Rho-associated protein serine/threonine kinase (ROCK), leading to phosphorylation of LIM kinase-2 (LIMK2) and inactivation of the actin depolymerization factor cofilin-1 (CFL1). Functional experiments recording cytoskeletal rearrangements in living cells showed that Wnt5A enhanced stress fiber formation as a consequence of reduced actin depolymerization. The antagonist Wnt inhibitory factor 1 (WIF1) that specifically interferes with the WIF domain of Ryk receptors prevented actin polymerization. Wnt5A disrupted β-catenin and VE-cadherin adherens junctions forming inter-endothelial gaps. Functional experiments targeting the endothelial monolayer integrity and live recording of trans-endothelial resistance revealed enhanced permeability of Wnt5A-treated HCAEC. Ryk silencing completely prevented Wnt5A-induced endothelial hyperpermeability. Wnt5A decreased wound healing capacity of HCAEC monolayers; this was restored by the ROCK inhibitor Y-27632. Here we show that Wnt5A acts on the vascular endothelium causing enhanced permeability through Ryk interaction and downstream ROCK/LIMK2/CFL1 signaling. Wnt5A/Ryk signaling might provide novel therapeutic strategies to prevent capillary leakage in systemic inflammation and septic shock.

Indexed as

Signal TransductionActinsAdherens JunctionsCell Membrane PermeabilityCell MovementCell SurvivalCofilin 1Coronary VesselsCytoskeletonElectric ImpedanceEndothelial CellsEnzyme ActivationGene Expression ProfilingGenome, HumanHumansInterleukin-1betaActinsCFL1 protein, humanCofilin 1Interleukin-1betaLIMK2 protein, humanLim KinasesProtein Kinase InhibitorsReceptor Protein-Tyrosine KinasesReceptors, Cell Surfacerho-Associated KinasesRYK protein, humanWnt-5a Proteinendotheliumsepsissystemic inflammationvascular permeabilityWnt5A

Identifiers

PMID27159116
PMCPMC5308226
OpenAlexW2345520399

What OpenQuestion holds

Textmetadata
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.