Evidence map›Paper›PMID 36835220›Full record

ArticleInternational journal of molecular sciences2023

Inhibition of Xanthine Oxidase Protects against Diabetic Kidney Disease through the Amelioration of Oxidative Stress via VEGF/VEGFR Axis and NOX-FoxO3a-eNOS Signaling Pathway.

Keum-Jin Yang, Won Jung Choi, Yoon-Kyung Chang, Cheol Whee Park, Suk Young Kim, Yu Ah Hong

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
5.8field-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

26 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.

  1. Pooled it
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  4. Article
  5. Article
  6. Review
  7. Current issues in molecular biology · 2026
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  9. Review
  10. Mechanism ofRenal failure · 2025
    Article
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  12. Article
  13. Observational
  14. Article
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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

6 authors at 2 institutions in 1 country.

Keum-Jin YangClinical Research Institute, Daejeon St. Mary's Hospital, 64, Daeheung-ro, Jung-gu, Daejeon 34943, Republic of Korea.
Won Jung ChoiDivision of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea.ORCID 0000-0001-8953-1059
Yoon-Kyung ChangDivision of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea.ORCID 0000-0003-4193-2034
Cheol Whee ParkDivision of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea.
Suk Young KimDivision of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea.
Yu Ah HongDivision of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea.ORCID 0000-0001-7856-4955
Catholic University of Korea · KRThe Catholic University of Korea Daejeon St. Mary's Hospital · KR

Funding

Catholic Medical Center Research Foundation the program year of 2018Clinical Research Institute of Daejeon St. Mary's Hospital CMCDJ-P-2020-012National Research Foundation of Korea 2018R1C1B5045006, 2021R1C1C1012208
6 · The paper itself

Abstract

Xanthine oxidase (XO) is an important source of reactive oxygen species. This study investigated whether XO inhibition exerts renoprotective effects by inhibiting vascular endothelial growth factor (VEGF) and NADPH oxidase (NOX) in diabetic kidney disease (DKD). Febuxostat (5 mg/kg) was administered to streptozotocin (STZ)-treated 8-week-old male C57BL/6 mice via intraperitoneal injection for 8 weeks. The cytoprotective effects, its mechanism of XO inhibition, and usage of high-glucose (HG)-treated cultured human glomerular endothelial cells (GECs) were also investigated. Serum cystatin C, urine albumin/creatinine ratio, and mesangial area expansion were significantly improved in febuxostat-treated DKD mice. Febuxostat reduced serum uric acid, kidney XO levels, and xanthine dehydrogenase levels. Febuxostat suppressed the expression of VEGF mRNA, VEGF receptor (VEGFR)1 and VEGFR3, NOX1, NOX2, and NOX4, and mRNA levels of their catalytic subunits. Febuxostat caused downregulation of Akt phosphorylation, followed by the enhancement of dephosphorylation of transcription factor forkhead box O3a (FoxO3a) and the activation of endothelial nitric oxide synthase (eNOS). In an in vitro study, the antioxidant effects of febuxostat were abolished by a blockade of VEGFR1 or VEGFR3 via NOX-FoxO3a-eNOS signaling in HG-treated cultured human GECs. XO inhibition attenuated DKD by ameliorating oxidative stress through the inhibition of the VEGF/VEGFR axis. This was associated with NOX-FoxO3a-eNOS signaling.

Indexed as

Diabetic NephropathiesXanthine OxidaseAnimalsEndothelial CellsFebuxostatHumansMaleMiceMice, Inbred C57BLNADPH OxidasesNitric Oxide Synthase Type IIIOxidative StressRNA, MessengerSignal TransductionUric AcidVascular Endothelial Growth Factor AFebuxostatNADPH OxidasesNitric Oxide Synthase Type IIIRNA, MessengerUric AcidVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsXanthine Oxidasediabetic kidney diseaseNADPH oxidaseoxidative stressVEGFxanthine oxidase

Identifiers

PMID36835220
PMCPMC9961241
OpenAlexW4320920676

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.