Evidence map›Paper›PMID 27327585›Full record

ArticleInvestigative ophthalmology & visual science2016

Proangiogenic Interactions of Vascular Endothelial MMP14 With VEGF Receptor 1 in VEGFA-Mediated Corneal Angiogenesis.

Kyu-Yeon Han, Jin-Hong Chang, Hyun Lee, Dimitri T Azar

Open access · goldAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
6.5field-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

25 citing papers in PubMed, 61 citations in OpenAlex.

  1. Article
  2. Article
  3. Matrix Metalloproteinase 14 in Corneal Neovascularization.International journal of molecular sciences · 2026
    Review
  4. Selective Degradation and Inhibition of SARS-CoV-2 3CLInternational journal of molecular sciences · 2025
    Article
  5. Review
  6. Review
  7. Article
  8. Available Therapeutic Options for Corneal Neovascularization: A Review.International journal of molecular sciences · 2024
    Review
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  10. Article
  11. Article
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  13. Review
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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 1 institution in 1 country.

Kyu-Yeon HanDepartment of Ophthalmology and Visual Sciences Illinois Eye and Ear Infirmary, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States.
Jin-Hong ChangDepartment of Ophthalmology and Visual Sciences Illinois Eye and Ear Infirmary, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States.
Hyun LeeCenter for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois, United States.
Dimitri T AzarDepartment of Ophthalmology and Visual Sciences Illinois Eye and Ear Infirmary, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States.
University of Illinois Chicago · US

Funding

Translational Core for Therapeutic and Diagnostic DevelopmentP30EY001792 · NEI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MCANANY, JAMES JASON · 1985 to 2025
$14.8M
METALLOPROTEINASE EXPRESSION IN CORNEAL WOUNDSR01EY010101 · NEI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI AZAR, DIMITRI T · 1999 to 2020
$6.5M
VEGFR2 Modulates Corneal Angiogenesis and LymphangiogenesisR21EY023691 · NEI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI CHANG, JIN-HONG · 2013 to 2014
$435k
NEI NIH HHS P30 EY001792NEI NIH HHS R01 EY010101NEI NIH HHS R21 EY023691
6 · The paper itself

Abstract

purposeMatrix metalloproteinase 14 (MMP14) has been shown to be required for corneal angiogenesis. We hypothesized that the proangiogenic activity of MMP14 may be based on its selective binding to, and cleaving of, vascular endothelial growth factor receptor 1 (VEGFR1), but not VEGFR2 or VEGFR3.

methodsRecombinant human (rh)VEGFR1, R2, and R3 were incubated with human MMP14, and the reaction mixtures were analyzed by SDS-PAGE and Coomassie blue staining. Surface plasmon resonance was used to determine the equilibrium constants (KD) for binding between MMP14 and VEGFA versus rhVEGFR1, R2, and R3. Extracellular signal-regulated kinase (ERK) phosphorylation was assayed in vascular endothelial cells after incubation with VEGF and various concentrations of MMP14. Ex vivo aortic ring tube formation assays and VEGFA micropocket corneal neovascularization assays were performed using Flk1Cre/Flk1mCherry/MMP14lox and Flk1mCherry/MMP14lox control mice.

resultsMaxtrix metalloproteinase 14 increased VEGFA-induced ERK phosphorylation in a time- and concentration-dependent manner in vascular endothelial cells. Aortic ring assays showed diminished vessel sprouting in vitro in response to VEGFA, but not to basic fibroblast growth factor, in mice with conditional deletion of vascular MMP14 (Flk1creMMP14lox) compared with that in MMP14lox control mice. In addition, diminished VEGFA-induced corneal angiogenesis was seen in flk1creMMP14lox mice compared with MMP14lox mice in vivo.

conclusionsOur findings indicate that VEGFR1 interaction with MMP14 and the enzymatic activity of MMP14 are necessary for VEGFA-induced angiogenesis. Additionally, selective cleavage of VEGFR1 by MMP14 may play an important role in VEGFA-induced corneal angiogenesis.

Indexed as

AnimalsCell ProliferationCorneaCorneal NeovascularizationDisease Models, AnimalEndothelial CellsFibroblast Growth FactorsHumansMAP Kinase Signaling SystemMatrix Metalloproteinase 14MiceReceptors, Vascular Endothelial Growth FactorRetinal VesselsVascular Endothelial Growth Factor AFibroblast Growth FactorsMatrix Metalloproteinase 14MMP14 protein, humanReceptors, Vascular Endothelial Growth FactorVascular Endothelial Growth Factor A

Identifiers

PMID27327585
PMCPMC5993529
OpenAlexW2463790765

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.