Evidence map›Paper›PMID 28075016›Full record

ArticleJournal of cellular physiology2017

Modulation of long-term endothelial-barrier integrity is conditional to the cross-talk between Akt and Src signaling.

Fei Gao, Harika Sabbineni, Sandeep Artham, Payaningal R Somanath

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of cellular physiology, 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
1.9field-weighted citation impact, top 14% 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, 37 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

4 authors at 2 institutions in 2 countries.

Fei GaoClinical and Experimental Therapeutics, University of Georgia and Charlie Norwood VA Medical Center, Augusta, Georgia.
Harika SabbineniClinical and Experimental Therapeutics, University of Georgia and Charlie Norwood VA Medical Center, Augusta, Georgia.
Sandeep ArthamClinical and Experimental Therapeutics, University of Georgia and Charlie Norwood VA Medical Center, Augusta, Georgia.
Payaningal R SomanathClinical and Experimental Therapeutics, University of Georgia and Charlie Norwood VA Medical Center, Augusta, Georgia.
University of Georgia · USChongqing University · CN

Funding

Protein kinase B (Akt)-mediated pathway regulating endothelial-barrier functionR01HL103952 · NHLBI · UNIVERSITY OF GEORGIA · PI SHENOY, SOMANATH P RAMMOHAN · 2011 to 2015
$1.5M
NHLBI NIH HHS R01 HL103952
6 · The paper itself

Abstract

Although numerous studies have implicated Akt and Src kinases in vascular endothelial growth factor (VEGF) and Angiopoietin-1 (Ang-1)-induced endothelial-barrier regulation, a link between these two pathways has never been demonstrated. We determined the long-term effects of Akt inhibition on Src activity and vice versa, and in turn, on the human microvascular endothelial cell (HMEC) barrier integrity at the basal level, and in response to growth factors. Our data showed that Akt1 gene knockdown increases gap formation in HMEC monolayer at the basal level. Pharmacological inhibition of Akt, but not Src resulted in exacerbated VEGF-induced vascular leakage and impaired Ang-1-induced HMEC-barrier protection in vitro at 24 hr. Whereas inhibition of Akt had no effect on VEGF-induced HMEC gap formation in the short term, inhibition of Src blunted this process. In contrast, inhibition of Akt disrupted the VEGF and Ang-1 stabilized barrier integrity in the long-term while inhibition of Src did not. Interestingly, both long-term Akt inhibition and Akt1 gene knockdown in HMECs resulted in increased Tyr416 phosphorylation of Src. Treatment of HMECs with transforming growth factor-β1 (TGFβ1) that inhibited Akt Ser473 phosphorylation in the long-term, activated Src through increased Tyr416 phosphorylation and decreased HMEC-barrier resistance. The effect of TGFβ1 on endothelial-barrier breakdown was blunted in Akt1 deficient HMEC monolayers, where endothelial-barrier resistance was already impaired compared to the control. To our knowledge, this is the first report demonstrating a direct cross-talk between Akt and Src in endothelial-barrier regulation.

Indexed as

Capillary PermeabilitySignal TransductionAngiopoietin-1Cells, CulturedEndothelial CellsHumansPhosphorylationProtein Kinase InhibitorsProto-Oncogene Proteins c-aktRNA InterferenceSerinesrc-Family KinasesTime FactorsTransfectionTransforming Growth Factor beta1TyrosineAKT1 protein, humanAngiopoietin-1Protein Kinase InhibitorsProto-Oncogene Proteins c-aktSerinesrc-Family KinasesTransforming Growth Factor beta1TyrosineVascular Endothelial Growth Factor AAktendothelial-barrierSrcvascular permeabilityVE-cadherin

Identifiers

PMID28075016
PMCPMC5482788
OpenAlexW2571705430

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.