Evidence map›Paper›PMID 19906640›Full record

ArticleThe Journal of biological chemistry2010

Regulation of vascular endothelial growth factor (VEGF) splicing from pro-angiogenic to anti-angiogenic isoforms: a novel therapeutic strategy for angiogenesis.

Dawid G Nowak, Elianna Mohamed Amin, Emma S Rennel, Coralie Hoareau-Aveilla, Melissa Gammons, Gopinath Damodoran, Masatoshi Hagiwara, Steven J Harper, Jeanette Woolard, Michael R Ladomery and 1 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
131citing papers in PubMed, 1 pooled it
5.9field-weighted citation impact, top 3% 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

131 citing papers in PubMed, 1 synthesis or guideline pooled it, 217 citations in OpenAlex.

  1. La Tunisie medicale · 2024
    Pooled it
  2. Trial
  3. Review
  4. Review
  5. Review
  6. RNA Splicing as a Therapeutic Target in Cancer.Annual review of pharmacology and toxicology · 2026
    Review
  7. Beyond transcription: RNA-binding proteins steering angiogenesis.American journal of physiology. Heart and circulatory physiology · 2026
    Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
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  20. Article

71 more citing papers are in PubMed but not listed here.

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 3 institutions in 2 countries.

Dawid G NowakMicrovascular Research Laboratories, Bristol Heart Institute, Department of Physiology and Pharmacology, School of Veterinary Sciences, University of Bristol, Bristol BS2 8EJ, United Kingdom.
Elianna Mohamed Amin
Emma S Rennel
Coralie Hoareau-Aveilla
Melissa Gammons
Gopinath Damodoran
Masatoshi Hagiwara
Steven J Harper
Jeanette Woolard
Michael R Ladomery
David O Bates
University of Bristol · GBUniversity of the West of England · GBTokyo Medical and Dental University · JP

Funding

British Heart Foundation BS/06/005British Heart Foundation FS/04/09Cancer Research UK C11392/A10484Wellcome TrustWellcome Trust BS/06/005
6 · The paper itself

Abstract

Vascular endothelial growth factor (VEGF) is produced either as a pro-angiogenic or anti-angiogenic protein depending upon splice site choice in the terminal, eighth exon. Proximal splice site selection (PSS) in exon 8 generates pro-angiogenic isoforms such as VEGF(165), and distal splice site selection (DSS) results in anti-angiogenic isoforms such as VEGF(165)b. Cellular decisions on splice site selection depend upon the activity of RNA-binding splice factors, such as ASF/SF2, which have previously been shown to regulate VEGF splice site choice. To determine the mechanism by which the pro-angiogenic splice site choice is mediated, we investigated the effect of inhibition of ASF/SF2 phosphorylation by SR protein kinases (SRPK1/2) on splice site choice in epithelial cells and in in vivo angiogenesis models. Epithelial cells treated with insulin-like growth factor-1 (IGF-1) increased PSS and produced more VEGF(165) and less VEGF(165)b. This down-regulation of DSS and increased PSS was blocked by protein kinase C inhibition and SRPK1/2 inhibition. IGF-1 treatment resulted in nuclear localization of ASF/SF2, which was blocked by SPRK1/2 inhibition. Pull-down assay and RNA immunoprecipitation using VEGF mRNA sequences identified an 11-nucleotide sequence required for ASF/SF2 binding. Injection of an SRPK1/2 inhibitor reduced angiogenesis in a mouse model of retinal neovascularization, suggesting that regulation of alternative splicing could be a potential therapeutic strategy in angiogenic pathologies.

Indexed as

Alternative SplicingAngiogenesis InhibitorsAnimalsCell Line, TransformedDisease Models, AnimalEnzyme InhibitorsHumansInsulin-Like Growth Factor IMiceNuclear ProteinsProtein IsoformsProtein Serine-Threonine KinasesRetinal NeovascularizationRNA-Binding ProteinsRNA, MessengerSerine-Arginine Splicing FactorsAngiogenesis InhibitorsEnzyme Inhibitorsinsulin-like growth factor-1, mouseInsulin-Like Growth Factor INuclear ProteinsProtein IsoformsProtein Serine-Threonine KinasesRNA-Binding ProteinsRNA, MessengerSerine-Arginine Splicing FactorsSRPK1 protein, humanSrpk1 protein, mouseSRPK2 protein, humanSrpk2 protein, mouseVascular Endothelial Growth Factor Avascular endothelial growth factor A, mouseVEGFA protein, human

Identifiers

PMID19906640
PMCPMC2820781
OpenAlexW2096592500

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.