Evidence map›Paper›PMID 21567393›Full record

ArticleJournal of cellular physiology2012

Diabetic retinopathy and signaling mechanism for activation of matrix metalloproteinase-9.

Ghulam Mohammad, Renu A Kowluru

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of cellular physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
6.3field-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

48 citing papers in PubMed, 78 citations in OpenAlex.

  1. Article
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  10. Article
  11. Diabetes, metabolic syndrome and obesity : targets and therapy · 2021
    Article
  12. Article
  13. Review
  14. Matrix Metalloproteinases and Glaucoma Treatment.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2020
    Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Review
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

2 authors at 1 institution in 1 country.

Ghulam MohammadKresge Eye Institute, Wayne State University, Detroit, Michigan 48201, USA.
Renu A Kowluru
Wayne State University · US

Funding

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
NEI NIH HHS EY014370NEI NIH HHS EY017313NEI NIH HHS R01 EY014370NEI NIH HHS R01 EY017313
6 · The paper itself

Abstract

In the pathogenesis of diabetic retinopathy, H-Ras (a small molecular weight G-protein) and matrix metalloproteinase-9 (MMP9) act as pro-apoptotic, accelerating the apoptosis of retinal capillary cells, a phenomenon that predicts its development and the activation of MMP9 is under the control of H-Ras. The goal of this study is to elucidate the cellular mechanism by which H-Ras activates MMP9 culminating in the development of diabetic retinopathy. Using isolated retinal endothelial cells, the effect of regulation of H-Ras downstream signaling cascade, Raf-1, MEK, and ERK, was investigated on glucose-induced activation of MMP9. In vitro results were confirmed in the retina obtained from diabetic mice manipulated for MMP9 gene, and also in the retinal microvasculature obtained from human donors with diabetic retinopathy. Regulation of Raf-1/MEK/ERK by their specific siRNAs and pharmacologic inhibitors prevented glucose-induced activation of MMP9 in retinal endothelial cells. In MMP9-KO mice, diabetes had no effect on retinal MMP9 activation, and H-Ras/Raf-1/MEK signaling cascade remained normal. Similarly, donors with diabetic retinopathy had increased MMP9 activity in their retinal microvessels, the site of histopathology associated with diabetic retinopathy, and this was accompanied by activated H-Ras signaling pathway (Raf-1/ERK). Collectively, these results suggest that Ras/Raf-1/MEK/ERK cascade has an important role in the activation of retinal MMP9 resulting in the apoptosis of its capillary cells. Understanding the upstream mechanism responsible for the activation of MMP9 should help identify novel molecular targets for future pharmacological interventions to inhibit the development/progression of diabetic retinopathy.

Indexed as

AdultAgedAnimalsApoptosisDiabetic RetinopathyDisease Models, AnimalEnzyme ActivationHumansMaleMAP Kinase Signaling SystemMatrix Metalloproteinase 9MiceMice, Inbred C57BLMice, KnockoutMicrocirculationMiddle AgedMatrix Metalloproteinase 9Mmp9 protein, mouse

Identifiers

PMID21567393
PMCPMC3801274
OpenAlexW2083207610

What OpenQuestion holds

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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.