Evidence map›Paper›PMID 38909885›Full record

ArticleJournal of advanced research2025

WWP2 deletion aggravates acute kidney injury by targeting CDC20/autophagy axis.

Ran You, Yanwei Li, Yuteng Jiang, Dandan Hu, Menglei Gu, Wei Zhou, Shengnan Zhang, Mi Bai, Yunwen Yang, Yue Zhang and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
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

8 citing papers in PubMed.

  1. Article
  2. Research progress on biomarkers for acute kidney injury in children.Pediatric nephrology (Berlin, Germany) · 2026
    Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. The oncogenic role of EIF4A3/CDC20 axis in the endometrial cancer.Journal of molecular medicine (Berlin, Germany) · 2024
    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

13 authors.

Ran YouNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China; Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China.
Yanwei LiNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China; Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China; School of Medicine, Southeast University, Nanjing, China.
Yuteng JiangNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China; School of Medicine, Southeast University, Nanjing, China.
Dandan HuNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China; Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China.
Menglei GuNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China; Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China.
Wei ZhouNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China; Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China.
Shengnan ZhangNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China; Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China.
Mi BaiNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China; Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China.
Yunwen YangNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China; Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China.
Yue ZhangNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China; Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China.
Songming HuangNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China; Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China.
Zhanjun JiaNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China; Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China. Electronic address: jiazj72@hotmail.com.
Aihua ZhangNanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China; Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China; School of Medicine, Southeast University, Nanjing, China. Electronic address: zhaihua@njmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionAcute kidney injury (AKI) is associated with high morbidity and mortality rates. The molecular mechanisms underlying AKI are currently being extensively investigated. WWP2 is an E3 ligase that regulates cell proliferation and differentiation. Whether WWP2 plays a regulatory role in AKI remains to be elucidated.

objectivesWe aimed to investigate the implication of WWP2 in AKI and its underlying mechanism in the present study.

methodsWe utilized renal tissues from patients with AKI and established AKI models in global or tubule-specific knockout (cKO) mice strains to study WWP2's implication in AKI. We also systemically analyzed ubiquitylation omics and proteomics to decipher the underlying mechanism.

resultsIn the present study, we found that WWP2 expression significantly increased in the tubules of kidneys with AKI. Global or tubule-specific knockout of WWP2 significantly aggravated renal dysfunction and tubular injury in AKI kidneys, whereas WWP2 overexpression significantly protected tubular epithelial cells against cisplatin. WWP2 deficiency profoundly affected autophagy in AKI kidneys. Further analysis with ubiquitylation omics, quantitative proteomics and experimental validation suggested that WWP2 mediated poly-ubiquitylation of CDC20, a negative regulator of autophagy. CDC20 was significantly decreased in AKI kidneys, and selective inhibiting CDC20 with apcin profoundly alleviated renal dysfunction and tubular injury in the cisplatin model with or without WWP2 cKO, indicating that CDC20 may serve as a downstream target of WWP2 in AKI. Inhibiting autophagy with 3-methyladenine blocked apcin's protection against cisplatin-induced renal tubular cell injury. Activating autophagy by rapamycin significantly protected against cisplatin-induced AKI in WWP2 cKO mice, whereas inhibiting autophagy by 3-methyladenine further aggravated apoptosis in cisplatin-exposed WWP2 KO cells.

conclusionTaken together, our data indicated that the WWP2/CDC20/autophagy may be an essential intrinsic protective mechanism against AKI. Further activating WWP2 or inhibiting CDC20 may be novel therapeutic strategies for AKI.

Indexed as

Acute Kidney InjuryAutophagyUbiquitin-Protein LigasesAnimalsCisplatinDisease Models, AnimalHumansKidney TubulesMaleMiceMice, Inbred C57BLMice, KnockoutUbiquitinationCisplatinUbiquitin-Protein LigasesWWP2 protein, humanWwp2 protein, mouseAcute kidney injuryAutophagyCDC20Tubular epithelial cellsWWP2

Identifiers

PMID38909885
PMCPMC12126736

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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.