Evidence map›Paper›PMID 31117124›Full record

ArticleInvestigative ophthalmology & visual science2019

MMP14-Containing Exosomes Cleave VEGFR1 and Promote VEGFA-Induced Migration and Proliferation of Vascular Endothelial Cells.

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

Open access · goldAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 11% 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

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Article
  6. Matrix Metalloproteinase 14 in Corneal Neovascularization.International journal of molecular sciences · 2026
    Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Biodistribution of therapeutic extracellular vesicles.Extracellular vesicles and circulating nucleic acids · 2023
    Review
  15. Article
  16. Extracellular Vesicles in Corneal Fibrosis/Scarring.International journal of molecular sciences · 2022
    Review
  17. Review
  18. Chemoresistance TransmissionFrontiers in oncology · 2022
    Article
  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

3 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-Chicago, Chicago, Illinois, United States.
Jin-Hong ChangDepartment of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, College of Medicine, University of Illinois-Chicago, Chicago, Illinois, United States.
Dimitri T AzarDepartment of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, College of Medicine, University of Illinois-Chicago, Chicago, Illinois, United States.
University of Illinois Chicago · US

Funding

METALLOPROTEINASE EXPRESSION IN CORNEAL WOUNDSR01EY010101 · NEI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI AZAR, DIMITRI T · 1999 to 2020
$6.5M
NEI NIH HHS R01 EY010101
6 · The paper itself

Abstract

Purpose: Investigate the impact matrix metalloproteinase 14 (MMP14) delivered via exosomes produced by corneal fibroblasts on vascular endothelial growth factor receptor 1 (VEGFR1) cleavage on endothelial cells, and other key processes of angiogenesis. Methods: Proteolysis of VEGFR1 and R2 by the catalytic domain of MMP14 was investigated via immunocytochemistry with anti-VEGFR1, anti-VEGFR2, and anti-MMP14 antibodies. Exosomes were isolated via precipitation and serial ultracentrifugation from wild-type (WT) and MMP14 exon4-deficient corneal fibroblasts. Transmission electron microscopy and nanotracking analysis were used to characterize the isolated exosomes. The presence of MMP14 in exosomes from WT fibroblasts was confirmed by Western blotting. VEGFR1 cleavage upon treatment with WT-derived exosomes, Δexon4-derived exosomes, or the pan-MMP inhibitor GM60001 was examined via in vitro proteolysis analysis using recombinant mouse (rm) VEGFR1/R2. Endothelial cell migration and proliferation were investigated using a Boyden chamber assay and BrdU incorporation, respectively. Results: WT-derived exosomes specifically cleaved rmVEGFR1 in vitro, whereas Δexon4-derived exosomes did not. Treatment with the pan-MMP inhibitor GM6001 effectively inhibited VEGFR1 cleavage by WT-derived exosomes, confirming the role of MMP14 in this cleavage. WT-derived exosomes induced greater endothelial cell migration (P < 0.01) and proliferation (P < 0.5) compared to Δexon4-derived exosomes. Conclusions: MMP14-containing exosomes may be involved in the regulation of corneal neovascularization through degradation of VEGFR1 and VEGFA-induced endothelial cell proliferation and migration.

Indexed as

Cell MovementCell ProliferationCorneaEndothelial CellsExosomesHumansImmunohistochemistryMatrix Metalloproteinase 14Vascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1Matrix Metalloproteinase 14MMP14 protein, humanVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1

Identifiers

PMID31117124
PMCPMC6532701
OpenAlexW2946667430

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.