Evidence map›Paper›PMID 19422911›Full record

ArticleMatrix biology : journal of the International Society for Matrix Biology2009

Perlecan regulates developmental angiogenesis by modulating the VEGF-VEGFR2 axis.

Jason J Zoeller, John M Whitelock, Renato V Iozzo

Open access · greenAbstract read
In one paragraph

Article in Matrix biology : journal of the International Society for Matrix Biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
3.1field-weighted citation impact, top 9% 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

70 citing papers in PubMed, 124 citations in OpenAlex.

  1. Article
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  7. Biomimetic strategies for the deputization of proteoglycan functions.Frontiers in cell and developmental biology · 2024
    Review
  8. Review
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  10. Article
  11. Article
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  18. A functional outside-in signaling network of proteoglycans and matrix molecules regulating autophagy.Matrix biology : journal of the International Society for Matrix Biology · 2021
    Article
  19. Cerebrovascular development: mechanisms and experimental approaches.Cellular and molecular life sciences : CMLS · 2021
    Review
  20. Review

10 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

3 authors at 2 institutions in 2 countries.

Jason J ZoellerDepartment of Pathology, Anatomy and Cell Biology, and the Cancer Cell Biology and Signaling Program, Kimmel Cancer Center, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.
John M Whitelock
Renato V Iozzo
Thomas Jefferson University · USUNSW Sydney · AU

Funding

Alcohol Tissue InjuryT32AA007463 · NIAAA · THOMAS JEFFERSON UNIVERSITY · PI HOEK, JOANNES B, VADIGEPALLI, RAJANIKANTH · 1985 to 2021
$9.1M
NEOPLASTIC MODULATION OF PROTEOGLYCAN METABOLISMR01CA039481 · NCI · UNIVERSITY OF PENNSYLVANIA · PI IOZZO, RENATO V. · 1985 to 2020
$7.1M
The Biology of Perlecan in Cancer and AngiogenesisR01CA047282 · NCI · THOMAS JEFFERSON UNIVERSITY · PI IOZZO, RENATO V. · 1990 to 2019
$5.7M
Natural EGFR Antagonists and CancerR01CA120975 · NCI · THOMAS JEFFERSON UNIVERSITY · PI IOZZO, RENATO V. · 2007 to 2010
$942k
NCI NIH HHS R01 CA039481NCI NIH HHS R01 CA047282NCI NIH HHS R01 CA120975NCI NIH HHS R01 CA39481NCI NIH HHS R01 CA47282NIAAA NIH HHS T32 AA007463NIAAA NIH HHS T32 AA07463
6 · The paper itself

Abstract

Using the zebrafish, we previously identified a central function for perlecan during angiogenic blood vessel development. Here, we explored the nature of perlecan function during developmental angiogenesis. A close examination of individual endothelial cell behavior revealed that perlecan is required for proper endothelial cell migration and proliferation. Because these events are largely mediated by VEGF-VEGFR2 signaling, we investigated the relationship between perlecan and the VEGF pathway. We discovered that perlecan knockdown caused an abnormal increase and redistribution of total VEGF-A protein suggesting that perlecan is required for the appropriate localization of VEGF-A. Importantly, we linked perlecan function to the VEGF pathway by efficiently rescuing the perlecan morphant phenotype by microinjecting VEGF-A(165) protein or mRNA. Combining the strategic localization of perlecan throughout the vascular basement membrane along with its growth factor-binding ability, we hypothesized a major role for perlecan during the establishment of the VEGF gradient which provides the instructive cues to endothelial cells during angiogenesis. In support of this hypothesis we demonstrated that human perlecan bound in a heparan sulfate-dependent fashion to VEGF-A(165). Moreover, perlecan enhanced VEGF mediated VEGFR2 activation of human endothelial cells. Collectively, our results indicate that perlecan coordinates developmental angiogenesis through modulation of VEGF-VEGFR2 signaling events. The identification of angiogenic factors, such as perlecan, and their role in vertebrate development will not only enhance overall understanding of the molecular basis of angiogenesis, but may also provide new insight into angiogenesis-based therapeutic approaches.

Indexed as

ZebrafishAnimalsAnimals, Genetically ModifiedEndothelial CellsGene Knockdown TechniquesHeparan Sulfate ProteoglycansHumansNeovascularization, PhysiologicPhenotypeProtein BindingRecombinant Fusion ProteinsSignal TransductionVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Heparan Sulfate ProteoglycansperlecanRecombinant Fusion ProteinsVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2

Identifiers

PMID19422911
PMCPMC2705690
OpenAlexW1971747634

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.