Evidence map›Paper›PMID 23144758›Full record

ArticlePloS one2012

NADPH oxidase 4 mediates insulin-stimulated HIF-1α and VEGF expression, and angiogenesis in vitro.

Dan Meng, Aihong Mei, Junxu Liu, Xueling Kang, Xianglin Shi, Ruizhe Qian, Sifeng Chen

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

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

56 citing papers in PubMed, 90 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 3 institutions in 2 countries.

Dan MengDepartment of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai, China. dmeng@fudan.edu.cn
Aihong Mei
Junxu Liu
Xueling Kang
Xianglin Shi
Ruizhe Qian
Sifeng Chen
Shanghai Medical College of Fudan University · CNTongji University · CNUniversity of Kentucky · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Acute intensive insulin therapy causes a transient worsening of diabetic retinopathy in type 1 diabetes patients and is related to VEGF expression. Reactive oxygen species (ROS) have been shown to be involved in HIF-1α and VEGF expression induced by insulin, but the role of specific ROS sources has not been fully elucidated. In this study we examined the role of NADPH oxidase subunit 4 (Nox4) in insulin-stimulated HIF-1α and VEGF expression, and angiogenic responses in human microvascular endothelial cells (HMVECs). Here we demonstrate that knockdown of Nox4 by siRNA reduced insulin-stimulated ROS generation, the tyrosine phosphorylation of IR-β and IRS-1, but did not change the serine phosphorylation of IRS-1. Nox4 gene silencing had a much greater inhibitory effect on insulin-induced AKT activation than ERK1/2 activation, whereas it had little effect on the expression of the phosphatases such as MKP-1 and SHIP. Inhibition of Nox4 expression inhibited the transcriptional activity of VEGF through HIF-1. Overexpression of wild-type Nox4 was sufficient to increase VEGF transcriptional activity, and further enhanced insulin-stimulated the activation of VEGF. Downregulation of Nox4 expression decreased insulin-stimulated mRNA and protein expression of HIF-1α, but did not change the rate of HIF-1α degradation. Inhibition of Nox4 impaired insulin-stimulated VEGF expression, cell migration, cell proliferation, and tube formation in HMVECs. Our data indicate that Nox4-derived ROS are essential for HIF-1α-dependent VEGF expression, and angiogenesis in vitro induced by insulin. Nox4 may be an attractive therapeutic target for diabetic retinopathy caused by intensive insulin treatment.

Indexed as

Blood VesselsCell MovementCell ProliferationCells, CulturedEnzyme ActivationExtracellular Signal-Regulated MAP KinasesGene ExpressionHumansHuman Umbilical Vein Endothelial CellsHypoglycemic AgentsHypoxia-Inducible Factor 1, alpha SubunitImmunoblottingInsulinInsulin Receptor Substrate ProteinsNADPH Oxidase 4NADPH OxidasesExtracellular Signal-Regulated MAP KinasesHypoglycemic AgentsHypoxia-Inducible Factor 1, alpha SubunitInsulinInsulin Receptor Substrate ProteinsIRS1 protein, humanNADPH Oxidase 4NADPH OxidasesNOX4 protein, humanProto-Oncogene Proteins c-aktReactive Oxygen SpeciesReceptor, InsulinTyrosineVascular Endothelial Growth Factor A

Identifiers

PMID23144758
PMCPMC3483150
OpenAlexW2113100031

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.