Evidence map›Paper›PMID 26860885›Full record

ArticleJournal of atherosclerosis and thrombosis2016

Crucial Role of the Aryl Hydrocarbon Receptor (AhR) in Indoxyl Sulfate-Induced Vascular Inflammation.

Shunsuke Ito, Mizuko Osaka, Takeo Edamatsu, Yoshiharu Itoh, Masayuki Yoshida

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

Article in Journal of atherosclerosis and thrombosis, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 2 pooled it
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

69 citing papers in PubMed, 2 syntheses or guidelines pooled it, 92 citations in OpenAlex.

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  14. Microphysiological Uremia Model Reveals Biophysical Potentiators of Vascular Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  15. Observational
  16. Review
  17. Indole metabolism and its role in diabetic macrovascular and microvascular complications.American heart journal plus : cardiology research and practice · 2025
    Review
  18. Review
  19. Article
  20. Article

9 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

5 authors at 2 institutions in 1 country.

Shunsuke ItoLife Science and Bioethics, Department of International Health Development, Tokyo Medical and Dental University.
Mizuko Osaka
Takeo Edamatsu
Yoshiharu Itoh
Masayuki Yoshida
Tokyo Medical and Dental University · JPKureha (Japan) · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimThe aryl hydrocarbon receptor (AhR), a ligand-inducible transcription factor mediating toxic effects of dioxins and uremic toxins, has recently emerged as a pathophysiological regulator of immune-inflammatory conditions. Indoxyl sulfate, a uremic toxin, is associated with cardiovascular disease in patients with chronic kidney disease and has been shown to be a ligand for AhR. The aim of this study was to investigate the potential role of AhR in indoxyl sulfate-induced leukocyte-endothelial interactions.

methodsEndothelial cell-specific AhR knockout (eAhR KO) mice were produced by crossing AhR floxed mice with Tie2 Cre mice. Indoxyl sulfate was administered for 2 weeks, followed by injection of TNF-α. Leukocyte recruitment to the femoral artery was assessed by intravital microscopy. Vascular endothelial cells were transfected with siRNA specific to AhR (siAhR) and treated with indoxyl sulfate, followed by stimulation with TNF-α.

resultsIndoxyl sulfate dramatically enhanced TNF-α-induced leukocyte recruitment to the vascular wall in control animals but not in eAhR KO mice. In endothelial cells, siAhR significantly reduced indoxyl sulfate-enhanced leukocyte adhesion as well as E-selectin expression, whereas the activation of JNK and nuclear factor-κB was not affected. A luciferase assay revealed that the region between －153 and －146 bps in the E-selectin promoter was responsible for indoxyl sulfate activity via AhR. Mutational analysis of this region revealed that activator protein-1 (AP-1) is responsible for indoxyl sulfate-triggered E-selectin expression via AhR.

conclusionAhR mediates indoxyl sulfate-enhanced leukocyte-endothelial interactions through AP-1 transcriptional activity, which may constitute a new mechanism of vascular inflammation in patients with renal disease.

Indexed as

AnimalsArteritisBasic Helix-Loop-Helix ProteinsBlotting, WesternCell AdhesionCells, CulturedChromatin ImmunoprecipitationElectrophoretic Mobility Shift AssayEndothelium, VascularE-SelectinFemaleHumansIndicanLeukocytesMaleMiceAhr protein, mouseBasic Helix-Loop-Helix ProteinsE-SelectinIndicanNF-kappa BReactive Oxygen SpeciesReceptors, Aryl Hydrocarbon

Identifiers

PMID26860885
PMCPMC7399298
OpenAlexW2416054795

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.