Evidence map›Paper›PMID 27804998›Full record

ArticleScientific reports2016

Keap1 hypomorphism protects against ischemic and obstructive kidney disease.

Roderick J Tan, Dionysios V Chartoumpekis, Brittney M Rush, Dong Zhou, Haiyan Fu, Thomas W Kensler, Youhua Liu

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

24 citing papers in PubMed, 38 citations in OpenAlex.

  1. Review
  2. Article
  3. NRF2 Dysregulation and Therapeutic Insights Across Chronic Kidney Diseases.International journal of molecular sciences · 2025
    Review
  4. Article
  5. Review
  6. NRF2 in kidney physiology and disease.Physiological reports · 2024
    Review
  7. Article
  8. T CellAntioxidants & redox signaling · 2023
    Article
  9. Article
  10. Targeting NRF2 to promote epithelial repair.Biochemical Society transactions · 2023
    Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Protective Role of Nrf2 in Renal Disease.Antioxidants (Basel, Switzerland) · 2020
    Review
  17. Roles of Nrf2 in Protecting the Kidney from Oxidative Damage.International journal of molecular sciences · 2020
    Review
  18. Article
  19. Ferroptosis and kidney diseases.International urology and nephrology · 2020
    Review
  20. Article
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 1 institution in 1 country.

Roderick J TanDepartment of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Dionysios V ChartoumpekisDepartment of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Brittney M RushDepartment of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Dong ZhouDepartment of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Haiyan FuDepartment of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Thomas W KenslerDepartment of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Youhua LiuDepartment of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
University of Pittsburgh · US

Funding

Single Nephron and MetabolomicsP30DK079307 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KLEYMAN, THOMAS R · 2008 to 2022
$13.4M
Targeting Nrf2 for Cancer ChemopreventionR35CA197222 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KENSLER, THOMAS W · 2015 to 2021
$6.7M
Tenancin-C as a major component of the fibrogenic nicheR01DK064005 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TAN, RODERICK JASON · 2003 to 2021
$5.1M
Renal and Epithelial Biology Training ProgramT32DK061296 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KLEYMAN, THOMAS R · 2002 to 2022
$3.1M
Beta-catenin Signaling and Podocyte DysfunctionR01DK091239 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LIU, YOUHUA · 2012 to 2015
$895k
NCI NIH HHS R35 CA197222NIDDK NIH HHS P30 DK079307NIDDK NIH HHS R01 DK064005NIDDK NIH HHS R01 DK091239NIDDK NIH HHS T32 DK061296
6 · The paper itself

Abstract

The Keap1/Nrf2 pathway is a master regulator of antioxidant, anti-inflammatory, and other cytoprotective mechanisms important in protection from kidney disease. For the first time in kidney disease, we describe the use of Keap1 hypomorphic mice, which possess Nrf2 hyperactivation. We exposed these mice and wild type controls to ischemia/reperfusion injury (IRI). The initial tubular injury at 24 hours post-IRI appeared to be unaffected, with the only observed difference being a decrease in inflammatory cytokine expression in the hypomorphs. However, we noted significant improvement in serum creatinine in the hypomorphs at 3 and 10 days after injury, and renal fibrosis was dramatically attenuated at the late timepoint. Assessment of Nrf2-regulated targets (GSTM1, GSTP1, NQO1) revealed higher expression in the hypomorphs at baseline. While injury tended to suppress these genes in wild-type mice, the suppression was attenuated or reversed in Keap1 hypomorphs, suggesting that protection in these mice was mediated by increased Nrf2 transcriptional activity. To assess the generalizability of our findings, we subjected the hypomorphs to unilateral ureteral obstruction (UUO) and again found significant protection and increased expression of Nrf2 targets. Overall, these results support the conclusion that the Nrf2 pathway is protective in a variety of kidney diseases.

Indexed as

AnimalsAntioxidantsGene Expression RegulationHumansKelch-Like ECH-Associated Protein 1Kidney DiseasesMaleMiceNF-E2-Related Factor 2Oxidative StressReperfusion InjurySignal TransductionUreteral ObstructionAntioxidantsKeap1 protein, mouseKelch-Like ECH-Associated Protein 1Nfe2l2 protein, mouseNF-E2-Related Factor 2

Identifiers

PMID27804998
PMCPMC5090361
OpenAlexW2549016817

What OpenQuestion holds

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Registered trials

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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.