Evidence map›Paper›PMID 26912277›Full record

ArticleScientific reports2016

Accumulation of p53 via down-regulation of UBE2D family genes is a critical pathway for cadmium-induced renal toxicity.

Jin-Yong Lee, Maki Tokumoto, Yasuyuki Fujiwara, Tatsuya Hasegawa, Yoshiyuki Seko, Akinori Shimada, Masahiko Satoh

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 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.5field-weighted citation impact, top 8% 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

13 citing papers in PubMed, 41 citations in OpenAlex.

  1. Molecular Mechanisms of Cadmium-Induced Toxicity and Its Modification.International journal of molecular sciences · 2025
    Review
  2. Review
  3. Article
  4. Article
  5. A soybean based-diet prevents Cadmium access to rat cerebellum, maintaining trace elements homeostasis and avoiding morphological alterations.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2023
    Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Digenic mutations of humanHuman genome variation · 2016
    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 4 institutions in 1 country.

Jin-Yong LeeLaboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, Aichi 464-8650, Japan.
Maki TokumotoLaboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, Aichi 464-8650, Japan.
Yasuyuki FujiwaraLaboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, Aichi 464-8650, Japan.
Tatsuya HasegawaDepartment of Environmental Biochemistry, Mount Fuji Research Institute, 5597-1 Kenmarubi, Kamiyoshida, Fujiyoshida, Yamanashi 403-0005, Japan.
Yoshiyuki SekoDepartment of Environmental Biochemistry, Mount Fuji Research Institute, 5597-1 Kenmarubi, Kamiyoshida, Fujiyoshida, Yamanashi 403-0005, Japan.
Akinori ShimadaLaboratory of Pathology, Department of Medical Technology, School of Life and Environmental Science, Azabu University, 1-17-71 Fuchinobe, Chuo-ku, Sagamihara, Kanagawa 252-5201, Japan.
Masahiko SatohLaboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, Aichi 464-8650, Japan.
Aichi Gakuin University · JPMount Fuji Research Institute · JPAzabu University · JPTokyo University of Pharmacy and Life Sciences · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chronic cadmium (Cd) exposure can induce renal toxicity. In Cd renal toxicity, p53 is thought to be involved. Our previous studies showed that Cd down-regulated gene expression of the UBE2D (ubiquitin-conjugating enzyme E2D) family members. Here, we aimed to define the association between UBE2D family members and p53-dependent apoptosis in human proximal tubular cells (HK-2 cells) treated with Cd. Cd increased intracellular p53 protein levels and decreased UBE2D2 and UBE2D4 gene expression via inhibition of YY1 and FOXF1 transcription factor activities. Double knockdown of UBE2D2 and UBE2D4 caused an increase in p53 protein levels, and knockdown of p53 attenuated not only Cd-induced apoptosis, but also Cd-induced apoptosis-related gene expression (BAX and PUMA). Additionally, the mice exposed to Cd for 6 months resulted in increased levels of p53 and induction of apoptosis in proximal tubular cells. These findings suggest that down-regulation of UBE2D family genes followed by accumulation of p53 in proximal tubular cells is an important mechanism for Cd-induced renal toxicity.

Indexed as

AnimalsApoptosisApoptosis Regulatory ProteinsBase Sequencebcl-2-Associated X ProteinBlotting, WesternCadmiumCell LineDown-RegulationFemaleForkhead Transcription FactorsHumansKidneyMiceMice, Inbred C57BLMicroscopy, FluorescenceApoptosis Regulatory ProteinsBBC3 protein, humanbcl-2-Associated X ProteinCadmiumForkhead Transcription FactorsFOXF1 protein, humanProto-Oncogene ProteinsRNA, Small InterferingTumor Suppressor Protein p53UBE2D2 protein, humanUbiquitin-Conjugating EnzymesYY1 Transcription Factor

Identifiers

PMID26912277
PMCPMC4766413
OpenAlexW2464213936

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.