Evidence map›Paper›PMID 41214892›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

TRIM56 Aggravates Cerebral Ischemia-Reperfusion Injury via Inhibiting KLF4-Activated Ferroptosis Signaling.

Qiangping Wang, Shuang Li, Man Li, Wenke Zhou, Jianqing Zhang, Zhenfu Wu, Zhaoqi Mao, Juan Wan, Xinhao Tang, Baoping Zheng and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–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

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. 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

16 authors.

Qiangping WangDepartment of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Shuang LiDepartment of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Man LiDepartment of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Wenke ZhouDepartment of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, 453100, China.
Jianqing ZhangDepartment of Central laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, China.
Zhenfu WuState Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute, Gannan Medical University, Ganzhou, 341000, China.
Zhaoqi MaoState Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute, Gannan Medical University, Ganzhou, 341000, China.
Juan WanState Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute, Gannan Medical University, Ganzhou, 341000, China.
Xinhao TangState Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute, Gannan Medical University, Ganzhou, 341000, China.
Baoping ZhengDepartment of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Qiang LiuDepartment of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Zhendong LiDepartment of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Xiaobing JiangDepartment of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Qingping WuDepartment of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Youfan YeDepartment of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.
Haijun WangDepartment of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.ORCID https://orcid.org/0000-0001-7137-4032

Funding

Ganzhou Science and Technology Innovation Talent Project - Youth Talent Project 2022CXRC9555National Natural Science Foundation of China 81201026Natural Science Foundation of Hubei Province 2021CFB549
6 · The paper itself

Abstract

Cerebral ischemia-reperfusion (I/R) injury often causes significant neuronal damage, neurological deficits, and long-term disability. This study investigates the role of tripartite motif-protein 56 (TRIM56) in cerebral I/R injury and elucidates the underlying mechanisms. Here, a significant increase in TRIM56 expression in the human brain, mouse brain, and primary neurons after cerebral I/R injury is first detected. TRIM56 knockout mice exhibit reduced neurological deficits and a diminished inflammatory response, with TRIM56 overexpression intensifying these effects. Mechanistic investigations demonstrate that TRIM56 promotes neuronal ferroptosis by directly interacting with Krüppel-like factor 4 (KLF4) and triggering its K48-linked ubiquitination-dependent degradation. Moreover, compound screening identifies farudodstat as a potential TRIM56 inhibitor to reduce I/R injury in vivo and in vitro. In conclusion, TRIM56 critically regulates neuronal damage during cerebral I/R injury, thereby presenting as a potential therapeutic target for reducing brain I/R injury. Novel therapeutic strategies inhibiting TRIM56 or its downstream signaling pathways may be developed to mitigate the devastating effects of I/R injury on neuronal survival and function.

Indexed as

Brain IschemiaFerroptosisKruppel-Like Transcription FactorsReperfusion InjuryTripartite Motif ProteinsUbiquitin-Protein LigasesAnimalsDisease Models, AnimalHumansKruppel-Like Factor 4MaleMiceMice, Inbred C57BLMice, KnockoutNeuronsSignal TransductionKLF4 protein, humanKlf4 protein, mouseKruppel-Like Factor 4Kruppel-Like Transcription FactorsTripartite Motif ProteinsUbiquitin-Protein Ligasescerebral I/R injuryE3 ubiquitin ligaseferroptosisinflammationTRIM56

Identifiers

PMID41214892
PMCPMC12884795

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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.