Evidence map›Paper›PMID 31316111›Full record

ArticleScientific reports2019

Activation of KEAP1/NRF2/P62 signaling alleviates high phosphate-induced calcification of vascular smooth muscle cells by suppressing reactive oxygen species production.

Ran Wei, Mayu Enaka, Yasuteru Muragaki

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 1 pooled it
4.9field-weighted citation impact, top 4% 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, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.

  1. Pooled it
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  5. Iron in Vascular Calcification: Pro-Calcific Agent or Protective Modulator?International journal of molecular sciences · 2025
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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

3 authors at 1 institution in 1 country.

Ran WeiDepartment of Pathology, Wakayama Medical University School of Medicine, Wakayama, Japan.
Mayu EnakaDepartment of Pathology, Wakayama Medical University School of Medicine, Wakayama, Japan.
Yasuteru MuragakiDepartment of Pathology, Wakayama Medical University School of Medicine, Wakayama, Japan. ymuragak@wakayama-med.ac.jp.
Wakayama Medical University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Vascular calcification is a complication of diseases and conditions such as chronic kidney disease, diabetes, and aging. Previous studies have demonstrated that high concentrations of inorganic phosphate (Pi) can induce oxidative stress and vascular smooth muscle cell calcification. KEAP1 (Kelch-like ECH-associated protein 1)/NF-E2-related factor 2 (NRF2) signaling has been shown to play important roles in protecting cells from oxidative stress. The current study aims to investigate the possible involvement of the KEAP1/NRF2/P62 -mediated antioxidant pathway in vascular calcification induced by high Pi levels. Exposure of vascular smooth muscle cells (VSMCs) to high Pi concentrations promoted the accumulation of reactive oxygen species (ROS) and the nuclear translocation of NRF2, along with an increase in P62 levels and a decrease in KEAP1 levels. A classic NRF2 activator, tert-butylhydroquinone (tBHQ), significantly decreased ROS levels and calcium deposition in VSMCs by promoting the nuclear translocation of NRF2 and upregulating P62 and KEAP1 expression. In contrast, silencing NRF2 and P62 with siRNAs increased the levels of ROS and calcium deposition in VSMCs. In conclusion, VSMC calcification can be alleviated by the activation of the KEAP1/NRF2/P62 antioxidative pathway, which could have a protective role when it is exogenously activated by tBHQ.

Indexed as

Cell LineFluoresceinsHumansHydroquinonesKelch-Like ECH-Associated Protein 1Muscle, Smooth, VascularMyocytes, Smooth MuscleNF-E2-Related Factor 2Oxidation-ReductionOxidative StressPhosphatesProtein TransportReactive Oxygen SpeciesRNA InterferenceRNA, Small InterferingSequestosome-1 Protein2-tert-butylhydroquinonediacetyldichlorofluoresceinFluoresceinsHydroquinonesKEAP1 protein, humanKelch-Like ECH-Associated Protein 1NFE2L2 protein, humanNF-E2-Related Factor 2PhosphatesReactive Oxygen SpeciesRNA, Small InterferingSequestosome-1 ProteinSQSTM1 protein, human

Identifiers

PMID31316111
PMCPMC6637199
OpenAlexW2960009181

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.