Evidence map›Paper›PMID 29468369›Full record

ArticleDiabetologia2018

Role of endoplasmic reticulum stress in 12/15-lipoxygenase-induced retinal microvascular dysfunction in a mouse model of diabetic retinopathy.

Khaled Elmasry, Ahmed S Ibrahim, Heba Saleh, Nehal Elsherbiny, Sally Elshafey, Khaled A Hussein, Mohamed Al-Shabrawey

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

Article in Diabetologia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
6.7field-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

40 citing papers in PubMed, 72 citations in OpenAlex.

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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

7 authors at 4 institutions in 2 countries.

Khaled ElmasryDepartment of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, 1460 Laney Walker Blvd., CB 2602, Augusta, GA, 30912, USA.
Ahmed S IbrahimDepartment of Ophthalmology and Culver Vision Discovery Institute, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Heba SalehDepartment of Oral Biology and Anatomy, Dental College of Georgia, Augusta University, Augusta, GA, USA.
Nehal ElsherbinyDepartment of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Sally ElshafeyDepartment of Oral Biology and Anatomy, Dental College of Georgia, Augusta University, Augusta, GA, USA.
Khaled A HusseinDepartment of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, 1460 Laney Walker Blvd., CB 2602, Augusta, GA, 30912, USA.
Mohamed Al-ShabraweyDepartment of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, 1460 Laney Walker Blvd., CB 2602, Augusta, GA, 30912, USA. malshabrawey@augusta.edu.
Augusta University · USMansoura University · EGDiscovery Institute · USNational Research Centre · EG

Funding

Role of lipoxygenase pathway in early microvascular dysfunction during diabetic rR01EY023315 · NEI · AUGUSTA UNIVERSITY · PI AL-SHABRAWEY, MOHAMED AL-SAYED · 2013 to 2017
$1.8M
NEI NIH HHS Grant 5R01EY023315-02 (MA).NEI NIH HHS R01 EY023315
6 · The paper itself

Abstract

aims/hypothesisOur earlier studies have established the role of 12/15-lipoxygenase (LO) in mediating the inflammatory reaction in diabetic retinopathy. However, the exact mechanism is still unclear. The goal of the current study was to identify the potential role of endoplasmic reticulum (ER) stress as a major cellular stress response in the 12/15-LO-induced retinal changes in diabetic retinopathy.

methodsWe used in vivo and in vitro approaches. For in vivo studies, experimental diabetes was induced in wild-type (WT) mice and 12/15-Lo (also known as Alox15) knockout mice (12/15-Lo

resultsDeletion of 12/15-Lo significantly attenuated diabetes-induced ER stress in mouse retina. In vitro, 15-HETE upregulated ER stress markers such as phosphorylated RNA-dependent protein kinase-like ER-regulated kinase (p-PERK), activating transcription factor 6 (ATF6) and protein disulfide isomerase (PDI) in HRECs. Inhibition of ER stress reduced 15-HETE-induced-leucocyte adhesion, VEGFR2 phosphorylation and NADPH oxidase expression/activity. However, inhibition of NADPH oxidase or deletion of Nox2 had no effect on ER stress induced by the 12/15-LO-derived metabolites both in vitro and in vivo. We also found that 15-HETE increases the intracellular calcium in HRECs. CONCLUSIONS/

interpretationER stress contributes to 12/15-LO-induced retinal inflammation in diabetic retinopathy via activation of NADPH oxidase and VEGFR2. Perturbation of calcium homeostasis in the retina might also play a role in linking 12/15-LO to retinal ER stress and subsequent microvascular dysfunction in diabetic retinopathy.

Indexed as

Endoplasmic Reticulum Stress12-Hydroxy-5,8,10,14-eicosatetraenoic AcidAnimalsApoptosisArachidonate 15-LipoxygenaseCalciumCatalytic DomainCell LineDiabetic RetinopathyEndoplasmic ReticulumEndothelial CellsHumansInflammationLeukocytesMaleMice12-Hydroxy-5,8,10,14-eicosatetraenoic AcidArachidonate 15-LipoxygenaseCalciumKDR protein, humanNADPH OxidasesVascular Endothelial Growth Factor Receptor-212/15-Lipoxygenase12-HETE15-HETEBioactive lipidsCalciumDiabetic retinopathyEicosanoidsER stressNADPH oxidaseVEGFR2

Identifiers

PMID29468369
PMCPMC5878142
OpenAlexW2792499654

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.