Evidence map›Paper›PMID 28124145›Full record

ArticleGraefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie2017

Role of oxidative stress in epigenetic modification of MMP-9 promoter in the development of diabetic retinopathy.

Renu A Kowluru, Yang Shan

Erratum issuedAbstract read
In one paragraph

Article in Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 2017. 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 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.5field-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

26 citing papers in PubMed, 48 citations in OpenAlex.

  1. Insulin Resistance and Inflammation.International journal of molecular sciences · 2026
    Review
  2. Review
  3. Review
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  6. Article
  7. Review
  8. Review
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  10. Diabetic Retinopathy and Cardiovascular Disease: A Literature Review.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023
    Review
  11. Review
  12. Article
  13. Article
  14. Diabetes, metabolic syndrome and obesity : targets and therapy · 2021
    Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

2 authors at 2 institutions in 1 country.

Renu A KowluruKresge Eye Institute, Wayne State University, Detroit, MI, 48201, USA. rkowluru@med.wayne.edu.
Yang ShanKresge Eye Institute, Wayne State University, Detroit, MI, 48201, USA.
Kresge Eye Institute · USWayne State University · US

Funding

Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3M
Role of Ras in Retinal Cell Death in DiabetesR01EY014370 · NEI · WAYNE STATE UNIVERSITY · PI KOWLURU, RENU A. · 2004 to 2023
$4.8M
Glycemic Control and Progression of Diabetic RetinopathyR01EY017313 · NEI · WAYNE STATE UNIVERSITY · PI KOWLURU, RENU A. · 2007 to 2022
$4.2M
NADPH Oxidase, Mitochondrial Dysfunction and Diabetic RetinopathyR01EY022230 · NEI · WAYNE STATE UNIVERSITY · PI KOWLURU, ANJANEYULU, KOWLURU, RENU A. · 2012 to 2022
$3.4M
NEI NIH HHS R01 EY014370NEI NIH HHS R01 EY017313NEI NIH HHS R01 EY022230NIDDK NIH HHS P30 DK020572
6 · The paper itself

Abstract

backgroundIn the pathogenesis of diabetic retinopathy, damaged retinal mitochondria accelerate apoptosis of retinal capillary cells, and regulation of oxidative stress by manipulating mitochondrial superoxide dismutase (SOD2) protects mitochondrial homeostasis and prevents the development of diabetic retinopathy. Diabetes also activates matrix metalloproteinase-9 (MMP-9), and activated MMP-9 damages retinal mitochondria. Recent studies have shown a dynamic DNA methylation process playing an important role in regulation of retinal MMP-9 transcription in diabetes; the aim of this study is to investigate the role of oxidative stress in MMP-9 transcription.

methodsThe effect of regulation of mitochondrial superoxide on DNA methylation of MMP-9 promoter region was investigated in retinal endothelial cells incubated in the presence or absence of a MnSOD mimetic MnTBAP, by quantifying the levels of 5 methyl cytosine (5mC) and hydroxyl-methyl cytosine (5hmC). The binding of DNA methylating, and of hydroxymenthylating enzymes (Dnmts and Tets, respectively), at MMP-9 promoter (by chromatin immunoprecipitation) was also evaluated. The in vitro results were confirmed in the retina of diabetic mice overexpressing SOD2.

resultsMnTBAP attenuated glucose-induced decrease in 5mC levels and increase on Dnmt1 binding at the MMP-9 promoter region. MnTBAP also ameliorated alterations in 5hmC levels and Tet binding, regulated MMP-9 transcription, and prevented mitochondrial damage. Similarly, mice overexpressing SOD2 were protected from diabetes-induced alteration in MMP-9 promoter methylation, and its transcription.

conclusionsThus, regulation of oxidative stress by pharmacologic/genetic approaches maintains retinal mitochondrial homeostasis by ameliorating epigenetic modifications in the MMP-9 promoter region.

Indexed as

Diabetes Mellitus, ExperimentalOxidative StressAnimalsApoptosisCattleCells, CulturedDiabetic RetinopathyDNADNA MethylationEnzyme-Linked Immunosorbent AssayEpigenomicsMatrix Metalloproteinase 9Mice, TransgenicMitochondriaPromoter Regions, GeneticReal-Time Polymerase Chain ReactionDNAMatrix Metalloproteinase 9Superoxide DismutaseDiabetic retinopathyDNA methylationEpigeneticsOxidative stress

Identifiers

PMID28124145
PMCPMC5395319
OpenAlexW2581765679

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.