Evidence map›Paper›PMID 27603666›Full record

ArticlePloS one2016

Src Family Kinases Modulate the Loss of Endothelial Barrier Function in Response to TNF-α: Crosstalk with p38 Signaling.

Alejandro P Adam, Anthony M Lowery, Nina Martino, Hiba Alsaffar, Peter A Vincent

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. 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
2.4field-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, 29 citations in OpenAlex.

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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

5 authors at 1 institution in 1 country.

Alejandro P AdamDepartment of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, United States of America.ORCID http://orcid.org/0000-0001-6285-7235
Anthony M LoweryDepartment of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, United States of America.
Nina MartinoDepartment of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, United States of America.
Hiba AlsaffarDepartment of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, United States of America.
Peter A VincentDepartment of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, United States of America.
Albany Medical Center Hospital · US

Funding

p120 Catenin and Endothelial Monolayer FunctionR01HL077870 · NHLBI · ALBANY MEDICAL COLLEGE · PI VINCENT, PETER A · 2006 to 2010
$1.8M
American Heart Association-American Stroke Association 13SDG17100110NHLBI NIH HHS R01 HL077870
6 · The paper itself

Abstract

Activation of Src Family Kinase (SFK) signaling is required for the increase in endothelial permeability induced by a variety of cytokines and growth factors. However, we previously demonstrated that activation of endogenous SFKs by expression of dominant negative C-terminal Src Kinase (DN-Csk) is not sufficient to decrease endothelial adherens junction integrity. Basal SFK activity has been observed in normal venular endothelia and was not associated with increased basal permeability. The basal SFK activity however was found to contribute to increased sensitivity of the venular endothelium to inflammatory mediator-induced leakage. How SFK activation achieves this is still not well understood. Here, we show that SFK activation renders human dermal microvascular endothelial cells susceptible to low doses of TNF-α. Treatment of DN-Csk-expressing cells with 50 pg/ml TNF-α induced a loss of TEER as well as drastic changes in the actin cytoskeleton and focal adhesion proteins. This synergistic effect was independent of ROCK or NF-κB activity. TNF-α-induced p38 signaling was required for the synergistic effect on barrier function, and activation of the p38 MAPK alone was also able to induce changes in permeability only in monolayers with active SFKs. These results suggest that the activation of endogenous levels of SFK renders the endothelial barrier more susceptible to low, physiologic doses of TNF-α through activation of p38 which leads to a loss of endothelial tight junctions.

Indexed as

Adherens JunctionsCell AdhesionCells, CulturedCSK Tyrosine-Protein KinaseEndothelial CellsGene Expression RegulationHumansNF-kappa Bp38 Mitogen-Activated Protein KinasesSignal Transductionsrc-Family KinasesTight JunctionsTumor Necrosis Factor-alphaCSK protein, humanCSK Tyrosine-Protein KinaseNF-kappa Bp38 Mitogen-Activated Protein Kinasessrc-Family KinasesTumor Necrosis Factor-alpha

Identifiers

PMID27603666
PMCPMC5014308
OpenAlexW2510428608

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.