Evidence map›Paper›PMID 24511132›Full record

ArticleJournal of the American Society of Nephrology : JASN2014

Genetic targeting or pharmacologic inhibition of NADPH oxidase nox4 provides renoprotection in long-term diabetic nephropathy.

Jay C Jha, Stephen P Gray, David Barit, Jun Okabe, Assam El-Osta, Tamehachi Namikoshi, Vicki Thallas-Bonke, Kirstin Wingler, Cedric Szyndralewiez, Freddy Heitz and 4 more

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

Article in Journal of the American Society of Nephrology : JASN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 191 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
191citing papers in PubMed, 1 pooled it
18.0field-weighted citation impact, top 1% 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

191 citing papers in PubMed, 1 synthesis or guideline pooled it, 348 citations in OpenAlex.

  1. Pooled it
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  17. Overexpression of adipose tissue ERα enhances PVAT anticontractility via NOX4-derived HAmerican journal of physiology. Heart and circulatory physiology · 2025
    Article
  18. Review
  19. Oxidative Stress in Renal Health.Antioxidants (Basel, Switzerland) · 2025
    Article
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131 more citing papers are in PubMed but not listed here.

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

14 authors at 6 institutions in 6 countries.

Jay C JhaDiabetic Complications Division, Juvenile Diabetes Research Foundation Danielle Alberti Memorial Centre for Diabetic Complications, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia; Department of Medicine, Monash University, Melbourne, Victoria, Australia;
Stephen P GrayDiabetic Complications Division, Juvenile Diabetes Research Foundation Danielle Alberti Memorial Centre for Diabetic Complications, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia;
David BaritDiabetic Complications Division, Juvenile Diabetes Research Foundation Danielle Alberti Memorial Centre for Diabetic Complications, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia;
Jun OkabeHuman Epigenetics Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia;
Assam El-OstaHuman Epigenetics Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia;
Tamehachi NamikoshiDiabetic Complications Division, Juvenile Diabetes Research Foundation Danielle Alberti Memorial Centre for Diabetic Complications, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia; Department of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Japan;
Vicki Thallas-BonkeDiabetic Complications Division, Juvenile Diabetes Research Foundation Danielle Alberti Memorial Centre for Diabetic Complications, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia;
Kirstin WinglerDepartment of Pharmacology, Cardiovascular Research Institute Maastricht, Faculty of Medicine, Health & Life Science, Maastricht University, Maastricht, The Netherlands;
Cedric SzyndralewiezGenkyotex SA, Geneva, Switzerland;
Freddy HeitzGenkyotex SA, Geneva, Switzerland;
Rhian M TouyzOttawa Hospital Research Institute, Ottawa, Ontario, Canada; and Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
Mark E CooperDiabetic Complications Division, Juvenile Diabetes Research Foundation Danielle Alberti Memorial Centre for Diabetic Complications, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia; Department of Medicine, Monash University, Melbourne, Victoria, Australia;
Harald H H W SchmidtDepartment of Pharmacology, Cardiovascular Research Institute Maastricht, Faculty of Medicine, Health & Life Science, Maastricht University, Maastricht, The Netherlands;
Karin A Jandeleit-DahmDiabetic Complications Division, Juvenile Diabetes Research Foundation Danielle Alberti Memorial Centre for Diabetic Complications, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia; Department of Medicine, Monash University, Melbourne, Victoria, Australia; karin.jandeleit-dahm@bakeridi.edu.au.
Baker Heart and Diabetes Institute · AUGenkyotex (Switzerland) · CHMaastricht University · NLKawasaki Medical School · JPMonash University · AUUniversity of Glasgow · GB

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

Diabetic nephropathy may occur, in part, as a result of intrarenal oxidative stress. NADPH oxidases comprise the only known dedicated reactive oxygen species (ROS)-forming enzyme family. In the rodent kidney, three isoforms of the catalytic subunit of NADPH oxidase are expressed (Nox1, Nox2, and Nox4). Here we show that Nox4 is the main source of renal ROS in a mouse model of diabetic nephropathy induced by streptozotocin administration in ApoE(-/-) mice. Deletion of Nox4, but not of Nox1, resulted in renal protection from glomerular injury as evidenced by attenuated albuminuria, preserved structure, reduced glomerular accumulation of extracellular matrix proteins, attenuated glomerular macrophage infiltration, and reduced renal expression of monocyte chemoattractant protein-1 and NF-κB in streptozotocin-induced diabetic ApoE(-/-) mice. Importantly, administration of the most specific Nox1/4 inhibitor, GKT137831, replicated these renoprotective effects of Nox4 deletion. In human podocytes, silencing of the Nox4 gene resulted in reduced production of ROS and downregulation of proinflammatory and profibrotic markers that are implicated in diabetic nephropathy. Collectively, these results identify Nox4 as a key source of ROS responsible for kidney injury in diabetes and provide proof of principle for an innovative small molecule approach to treat and/or prevent chronic kidney failure.

Indexed as

Diabetes Mellitus, ExperimentalDiabetic NephropathiesAlbuminuriaAnimalsApolipoproteins ECell Line, TransformedDisease Models, AnimalEnzyme InhibitorsExtracellular MatrixGene SilencingGlucoseHumansMacrophagesMaleMiceMice, KnockoutApolipoproteins EEnzyme InhibitorsGlucoseNADH, NADPH OxidoreductasesNADPH Oxidase 1NADPH Oxidase 4NADPH OxidasesNOX1 protein, humanNOX1 protein, mouseNOX4 protein, humanNox4 protein, mousePyrazolesPyrazolonesPyridinesPyridonesReactive Oxygen Speciessetanaxib

Identifiers

PMID24511132
PMCPMC4033375
OpenAlexW2098414680

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.