Evidence map›Paper›PMID 25910937›Full record

ArticleBiology open2015

VEGF-A isoform-specific regulation of calcium ion flux, transcriptional activation and endothelial cell migration.

Gareth W Fearnley, Alexander F Bruns, Stephen B Wheatcroft, Sreenivasan Ponnambalam

Open access · goldAbstract read
In one paragraph

Article in Biology open, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
0.9field-weighted citation impact, top 25% 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

15 citing papers in PubMed, 27 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Targeting EB3-IPAmerican journal of respiratory cell and molecular biology · 2023
    Article
  5. Article
  6. Monitoring VEGF-Stimulated Calcium Ion Flux in Endothelial Cells.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  7. Article
  8. Article
  9. Pharmaceutical biology · 2019
    Article
  10. Endothelial CaInternational journal of molecular sciences · 2019
    Review
  11. Article
  12. Review
  13. Molecular Pharmacology of VEGF-A Isoforms: Binding and Signalling at VEGFR2.International journal of molecular sciences · 2018
    Review
  14. Article
  15. Article
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.

Gareth W FearnleyEndothelial Cell Biology Unit, School of Molecular & Cellular Biology, LIGHT Laboratories, University of Leeds, Leeds LS2 9JT, UK.
Alexander F BrunsDivision of Cardiovascular & Diabetes Research, Faculty of Medicine & Health, LIGHT Laboratories, University of Leeds, Leeds LS2 9JT, UK.
Stephen B WheatcroftDivision of Cardiovascular & Diabetes Research, Faculty of Medicine & Health, LIGHT Laboratories, University of Leeds, Leeds LS2 9JT, UK.
Sreenivasan PonnambalamEndothelial Cell Biology Unit, School of Molecular & Cellular Biology, LIGHT Laboratories, University of Leeds, Leeds LS2 9JT, UK s.ponnambalam@leeds.ac.uk.
University of Leeds · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Vascular endothelial growth factor A (VEGF-A) regulates many aspects of vascular physiology such as cell migration, proliferation, tubulogenesis and cell-cell interactions. Numerous isoforms of VEGF-A exist but their physiological significance is unclear. Here we evaluated two different VEGF-A isoforms and discovered differential regulation of cytosolic calcium ion flux, transcription factor localisation and endothelial cell response. Analysis of VEGF-A isoform-specific stimulation of VEGFR2-dependent signal transduction revealed differential capabilities for isoform activation of multiple signal transduction pathways. VEGF-A165 treatment promoted increased phospholipase Cγ1 phosphorylation, which was proportional to the subsequent rise in cytosolic calcium ions, in comparison to cells treated with VEGF-A121. A major consequence of this VEGF-A isoform-specific calcium ion flux in endothelial cells is differential dephosphorylation and subsequent nuclear translocation of the transcription factor NFATc2. Using reverse genetics, we discovered that NFATc2 is functionally required for VEGF-A-stimulated endothelial cell migration but not tubulogenesis. This work presents a new mechanism for understanding how VEGF-A isoforms program complex cellular outputs by converting signal transduction pathways into transcription factor redistribution to the nucleus, as well as defining a novel role for NFATc2 in regulating the endothelial cell response.

Indexed as

CalciumCell migrationEndothelialNFATc2VEGF-A

Identifiers

PMID25910937
PMCPMC4467193
OpenAlexW2152264183

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.