Evidence map›Paper›PMID 24966171›Full record

ArticleMolecular biology of the cell2014

VEGF-A isoforms differentially regulate ATF-2-dependent VCAM-1 gene expression and endothelial-leukocyte interactions.

Gareth W Fearnley, Adam F Odell, Antony M Latham, Nadeem A Mughal, Alexander F Bruns, Nicholas J Burgoyne, Shervanthi Homer-Vanniasinkam, Ian C Zachary, Monica C Hollstein, Stephen B Wheatcroft and 1 more

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

21 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. Article
  3. SubvertingBiology · 2024
    Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Effects of Coconut Water on Retina in Diabetic Rats.Evidence-based complementary and alternative medicine : eCAM · 2020
    Article
  9. Article
  10. Review
  11. Article
  12. Alternative Splicing in Angiogenesis.International journal of molecular sciences · 2019
    Review
  13. Molecular Pharmacology of VEGF-A Isoforms: Binding and Signalling at VEGFR2.International journal of molecular sciences · 2018
    Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. 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

11 authors at 5 institutions in 2 countries.

Gareth W FearnleyEndothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom.
Adam F OdellEndothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom.
Antony M LathamEndothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom.
Nadeem A MughalEndothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, United KingdomLeeds Vascular Institute, Leeds General Infirmary, Leeds LS1 3EX, United Kingdom.
Alexander F BrunsDivision of Cardiovascular and Diabetes Research, Faculty of Medicine and Health, LIGHT Laboratories, University of Leeds, Leeds LS2 9JT, United Kingdom.
Nicholas J BurgoyneFios Genomics, Edinburgh EH16 4UX, United Kingdom.
Shervanthi Homer-VanniasinkamLeeds Vascular Institute, Leeds General Infirmary, Leeds LS1 3EX, United Kingdom.
Ian C ZacharyDivision of Cardiovascular Biology and Medicine, Rayne Institute, University College London, London, United Kingdom.
Monica C HollsteinGerman Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Stephen B WheatcroftDivision of Cardiovascular and Diabetes Research, Faculty of Medicine and Health, LIGHT Laboratories, University of Leeds, Leeds LS2 9JT, United Kingdom.
Sreenivasan PonnambalamEndothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom s.ponnambalam@leeds.ac.uk.
University of Leeds · GBLeeds General Infirmary · GBFios Genomics (United Kingdom) · GBGerman Cancer Research Center · DEUniversity College London · GB

Funding

British Heart Foundation RG/06/003/21131British Heart Foundation RG/11/11/29050Medical Research Council
6 · The paper itself

Abstract

Vascular endothelial growth factor A (VEGF-A) regulates many aspects of vascular physiology. VEGF-A stimulates signal transduction pathways that modulate endothelial outputs such as cell migration, proliferation, tubulogenesis, and cell-cell interactions. Multiple VEGF-A isoforms exist, but the biological significance of this is unclear. Here we analyzed VEGF-A isoform-specific stimulation of VCAM-1 gene expression, which controls endothelial-leukocyte interactions, and show that this is dependent on both ERK1/2 and activating transcription factor-2 (ATF-2). VEGF-A isoforms showed differential ERK1/2 and p38 MAPK phosphorylation kinetics. A key feature of VEGF-A isoform-specific ERK1/2 activation and nuclear translocation was increased phosphorylation of ATF-2 on threonine residue 71 (T71). Using reverse genetics, we showed ATF-2 to be functionally required for VEGF-A-stimulated endothelial VCAM-1 gene expression. ATF-2 knockdown blocked VEGF-A-stimulated VCAM-1 expression and endothelial-leukocyte interactions. ATF-2 was also required for other endothelial cell outputs, such as cell migration and tubulogenesis. In contrast, VCAM-1 was essential only for promoting endothelial-leukocyte interactions. This work presents a new paradigm for understanding how soluble growth factor isoforms program complex cellular outputs and responses by modulating signal transduction pathways.

Indexed as

MAP Kinase Signaling SystemActivating Transcription Factor 2Cell MovementCell ProliferationGene ExpressionHumansLeukocytesPhosphorylationProtein IsoformsVascular Cell Adhesion Molecule-1Vascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Activating Transcription Factor 2ATF2 protein, humanKDR protein, humanProtein IsoformsVascular Cell Adhesion Molecule-1Vascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2VEGFA protein, human

Identifiers

PMID24966171
PMCPMC4142621
OpenAlexW2045284607

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.