Evidence map›Paper›PMID 25187372›Full record

ArticleDiabetes2015

Deletion of placental growth factor prevents diabetic retinopathy and is associated with Akt activation and HIF1α-VEGF pathway inhibition.

Hu Huang, Jianbo He, Da'Kuawn Johnson, Yanhong Wei, Ying Liu, Shuang Wang, Gerard A Lutty, Elia J Duh, Richard D Semba

Erratum issuedOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 93 papers.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed
7.8field-weighted citation impact, top 2% 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

93 citing papers in PubMed, 152 citations in OpenAlex.

  1. Review
  2. Review
  3. Lipoxin A 4 (LXA 4 ) for diabetic retinopathy (DR).Indian journal of ophthalmology · 2026
    Article
  4. Article
  5. Review
  6. Review
  7. Molecular stress and neurovascular injury in the diabetic retina.The Journal of clinical investigation · 2026
    Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Review
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  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 3 countries.

Hu HuangWilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD hhuang27@jhmi.edu.
Jianbo HeWilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD Guangxi Tumor Hospital and Institute, Nanning, Guangxi, China.
Da'Kuawn JohnsonWilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD.
Yanhong WeiWilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD.
Ying LiuWilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD Aier Eye Hospital, Changsha, Hunan, China.
Shuang WangWilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD China Japan Union Hospital, Changchun, Jilin, China.
Gerard A LuttyWilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD.
Elia J DuhWilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD.
Richard D SembaWilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD.
Johns Hopkins Medicine · USJohns Hopkins University · USVIB-KU Leuven Center for Microbiology · BE

Funding

Regulation of diabetic retinopathy by Nrf2R01EY022383 · NEI · JOHNS HOPKINS UNIVERSITY · PI DUH, ELIA J · 2012 to 2020
$3.8M
Potential target molecules for ischemic retinopathiesR01EY017164 · NEI · JOHNS HOPKINS UNIVERSITY · PI LUTTY, GERARD ANTHONY · 2007 to 2011
$1.9M
Systemic complement and age-related macular degeneration.R01EY024596 · NEI · JOHNS HOPKINS UNIVERSITY · PI SEMBA, RICHARD D · 2014 to 2016
$1.6M
NEI NIH HHS EY017164NEI NIH HHS EY022383NEI NIH HHS R01 EY017164NEI NIH HHS R01 EY022383NEI NIH HHS R01 EY024596
6 · The paper itself

Abstract

A new diabetic mouse strain, the Akita.PlGF knockout ((-/-)), was generated to study the role of placental growth factor (PlGF) in the pathogenesis of diabetic retinopathy (DR). PlGF deletion did not affect blood glucose but reduced the body weight of Akita.PlGF(-/-) mice. Diabetes-induced retinal cell death, capillary degeneration, pericyte loss, and blood-retinal barrier breakdown were prevented in these mice. Protein expression of PlGF was upregulated by diabetes, particularly in vascular cells. Diabetes-induced degradation of ZO-1 and VE-cadherin was reversed due to PlGF deficiency; their expression was correlated with that of sonic hedgehog and angiopoietin-1. PlGF deletion in Akita mice resulted in an increased Akt phosphorylation. Diabetes-activated hypoxia-inducible factor (HIF)1α-vascular endothelial growth factor (VEGF) pathway, including expression of HIF1α, VEGF, VEGFR1-3, and the extent of phospho (p)-VEGFR1, p-VEGFR2, and p-endothelial nitric oxide synthase, was inhibited in the retinas of diabetic PlGF(-/-) mice. However, expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, CD11b, and CD18 was not inhibited by PlGF deletion, nor was retinal leukostasis. These results suggest that PlGF is critical for the development of DR, and its genetic deletion protects the retina from diabetic damage. Protective mechanisms are associated with Akt activation and HIF1α-VEGF pathway inhibition, but independent of retinal leukostasis in the retinas of diabetic PlGF(-/-) mice.

Indexed as

Disease Models, AnimalMice, KnockoutAnimalsAntigens, CDApoptosisBlood GlucoseBody WeightCadherin 5CadherinsCapillariesDiabetic RetinopathyFemaleHypoxia-Inducible Factor 1, alpha SubunitMaleMice, Inbred C57BLNeovascularization, PathologicAntigens, CDBlood GlucoseCadherin 5CadherinsHif1a protein, mouseHypoxia-Inducible Factor 1, alpha SubunitPgf protein, mousePlacenta Growth FactorPregnancy ProteinsProto-Oncogene Proteins c-aktTjp1 protein, mouseVascular Endothelial Growth Factor Avascular endothelial growth factor A, mouseZonula Occludens-1 Protein

Identifiers

PMID25187372
PMCPMC4274802
OpenAlexW2109751424

What OpenQuestion holds

Textmetadata
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.