Evidence map›Paper›PMID 40586264›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

Acod1 Promotes PAD4 Ubiquitination via UBR5 Alkylation to Modulate NETosis and Exert Protective Effects in Sepsis.

Huifan Liu, Guoqing Jing, Shujuan Wu, Min Yuan, Yingyue Dong, Xue Chen, Huimin Zhou, Hailong Gong, Jing Zuo, Xiaojing Wu and 1 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. 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
–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

13 citing papers in PubMed.

  1. Review
  2. Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026
    Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. Itaconate modifications: Mechanisms and applications.Journal of intensive medicine · 2026
    Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. 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

11 authors.

Huifan LiuDepartment of Anesthesiology, Research Centre of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, China.ORCID https://orcid.org/0000-0001-5157-9700
Guoqing JingDepartment of Anesthesiology, Research Centre of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, China.
Shujuan WuDepartment of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Min YuanDepartment of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, China.
Yingyue DongDepartment of Anesthesiology, Research Centre of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, China.
Xue ChenDepartment of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, China.
Huimin ZhouDepartment of Anesthesiology, Research Centre of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, China.
Hailong GongDepartment of Anesthesiology, Research Centre of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, China.
Jing ZuoDepartment of Anesthesiology, Research Centre of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, China.
Xiaojing WuDepartment of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, China.
Xuemin SongDepartment of Anesthesiology, Research Centre of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, China.ORCID https://orcid.org/0009-0009-5788-7857

Funding

China Postdoctoral Science Foundation 2024M752483China Postdoctoral Science Foundation 2024M752489National Natural Science Foundation of China 82172144National Natural Science Foundation of China 82371370National Natural Science Foundation of China 82372156Postdoctoral Fellowship Program of CPSF GZC20231980Postdoctor Project of Hubei Province 2024HBBHCXA068
6 · The paper itself

Abstract

Neutrophil extracellular traps (NETs) are reticular structures released by neutrophils, and the process of their formation is called NETosis. NETs play a key role in the pathological process of sepsis. However, the specific regulatory mechanism has not been fully clarified. This study finds that the levels of NETs in peripheral blood are significantly elevated in clinical sepsis patients and cecal ligation and puncture (CLP) mouse models, and the expression of Acod1 is closely related to the generation of NETs. Acod1 knockout led to a further increase in NETs levels in CLP mice, aggravated the inflammatory response, worsened organ damage, and reduced the survival rate. Further studies indicate that E3 ubiquitin ligase UBR5 interacts with PAD4 (one of the core proteins for NETs generation). Acod1/itaconate (ITA) enhanced the enzymatic activity of UBR5 through alkylation modification, promoting the K48-linked polyubiquitination and degradation of PAD4, thereby inhibiting NETosis. In conclusion, this study combines transcriptomics, metabolomics, genetic engineering, and co-immunoprecipitation techniques to reveal the molecular mechanism of Acod1/ITA in regulating NETs, providing new potential targets and theoretical basis for the treatment of sepsis.

Indexed as

Extracellular TrapsProtein-Arginine Deiminase Type 4SepsisUbiquitin-Protein LigasesAlkylationAnimalsDisease Models, AnimalFemaleHumansMaleMiceMice, Inbred C57BLMice, KnockoutNeutrophilsUbiquitinationpeptidylarginine deiminase 4, mouseProtein-Arginine Deiminase Type 4Ubiquitin-Protein LigasesUBR5 protein, humanAcod1Neutrophil extracellular trapsNeutrophilsSepsisUbiquitination

Identifiers

PMID40586264
PMCPMC12463110

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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.