Evidence map›Paper›PMID 39603205›Full record

ArticleRedox biology2024

Redox-sensitive epigenetic activation of SUV39H1 contributes to liver ischemia-reperfusion injury.

Zilong Li, Jichen Li, Meng Wu, Zexin Li, Jiawen Zhou, Yunjie Lu, Yong Xu, Lei Qin, Zhiwen Fan

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Redox biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
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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

9 authors.

Zilong LiState Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing, China; Institute of Brain Science and Brain-inspired Research, Shandong First Medical University, Jinan, China. Electronic address: zlli@sdfmu.edu.cn.
Jichen LiState Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing, China.
Meng WuState Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing, China.
Zexin LiState Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing, China.
Jiawen ZhouState Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing, China.
Yunjie LuDepartment of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Soochow University, Suzhou, China.
Yong XuState Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing, China; Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Translational Medicine, Nanjing Medical University, Nanjing, China; Institute of Biomedical Research, College of Agriculture and Biology, Liaocheng University, Liaocheng, China. Electronic address: yjxu@cpu.edu.cn.
Lei QinDepartment of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Soochow University, Suzhou, China. Electronic address: qinlei@suda.edu.cn.
Zhiwen FanDepartment of Pathology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China. Electronic address: fanzhiwenfff@126.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Liver ischemia-reperfusion (I/R) injury is a clinically relevant pathophysiological process that determines the effectiveness of life-saving liver transplantation, to which aberrant ROS accumulation plays a key role. In the present study we investigated the role of SUV39H1, a lysine methyltransferases, in this process focusing on regulatory mechanism and translational potential. We report that SUV39H1 expression was up-regulated in the liver tissues of mice subjected to ischemia-reperfusion and in hepatocytes exposed to hypoxia-reoxygenation (H/R) in a redox-sensitive manner. Mechanistically, coactivator associated arginine methyltransferases 1 (CARM1) mediated redox-sensitive Suv39h1 trans-activation by promoting histone H3R17 methylation. Consistently, pharmaceutical CARM1 inhibition attenuated liver I/R injury. In addition, global or hepatocyte conditional Suv39h1 KO mice were protected from liver I/R injury. RNA-seq revealed that aldehyde dehydrogenase 1 family 1a (Aldh1a1) as a novel target for SUV39H1. SUV39H1 directly bound to the Aldh1a1 promoter and repressed Aldh1a1 transcription in H/R-challenged hepatocytes. ALDH1A1 silencing abrogated the protective effects of SUV39H1 deficiency on H/R-inflicted injuries whereas ALDH1A1 over-expression mitigated liver I/R injury in mice. Importantly, administration of a small-molecule SUV39H1 inhibitor achieved similar hepatoprotective effects as SUV39H1 deletion. Finally, increased Suv39h1 expression and decreased Aldh1a1 expression were observed in liver I/R specimens in humans. In conclusion, our data uncover a regulatory role for SUV39H1 in liver I/R injury and serve as proof-of-concept that targeting the SUV39H1-ALDH1A1 axis might be considered as a reasonable approach for the intervention of liver I/R injury.

Indexed as

Epigenesis, GeneticLiverMethyltransferasesOxidation-ReductionReperfusion InjuryRepressor ProteinsAnimalsHepatocytesHumansMaleMiceMice, KnockoutProtein-Arginine N-Methyltransferasescoactivator-associated arginine methyltransferase 1MethyltransferasesProtein-Arginine N-MethyltransferasesRepressor ProteinsSuv39h1 protein, mouseEpigeneticsHepatocyteIschemia-reperfusionRedox homeostasisTranscriptional regulation

Identifiers

PMID39603205
PMCPMC11635714

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.