Evidence map›Paper›PMID 40598772›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025

miR-375 protects against acetaminophen-induced acute liver failure by orchestrating pharmacogene expression.

Yi Wang, Jinghua Liu, Sha Zhu, Shiliang Hu, Xiupeng Chen, Elisabet Mandon, Ngoc Tam Tran, Songbo Zhang, Yangran Qi, Hong Ma and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

19 authors.

Yi WangDepartment of Pathophysiology, West China College of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan, P.R. China; Horae Gene Therapy Center, UMass Chan Medical School, Worcester, MA, USA.
Jinghua LiuHorae Gene Therapy Center, UMass Chan Medical School, Worcester, MA, USA; Viral Vector Core, UMass Chan Medical School, Worcester, MA, USA; Department of Genetics and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.
Sha ZhuHorae Gene Therapy Center, UMass Chan Medical School, Worcester, MA, USA; Department of Genetics and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.
Shiliang HuHorae Gene Therapy Center, UMass Chan Medical School, Worcester, MA, USA; Department of Genetics and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.
Xiupeng ChenHorae Gene Therapy Center, UMass Chan Medical School, Worcester, MA, USA; Department of Genetics and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.
Elisabet MandonHorae Gene Therapy Center, UMass Chan Medical School, Worcester, MA, USA; Department of Genetics and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA; Department of Microbiology, UMass Chan Medical School, Worcester, MA, USA.
Ngoc Tam TranHorae Gene Therapy Center, UMass Chan Medical School, Worcester, MA, USA; Department of Genetics and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.
Songbo ZhangDepartment of Breast Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China.
Yangran QiDepartment of Pathophysiology, West China College of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan, P.R. China.
Hong MaHorae Gene Therapy Center, UMass Chan Medical School, Worcester, MA, USA; Viral Vector Core, UMass Chan Medical School, Worcester, MA, USA.
Ran HeHorae Gene Therapy Center, UMass Chan Medical School, Worcester, MA, USA; Viral Vector Core, UMass Chan Medical School, Worcester, MA, USA.
Yu CaoDepartment of Emergency Medicine, Laboratory of Emergency Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, China.
Qin SuHorae Gene Therapy Center, UMass Chan Medical School, Worcester, MA, USA; Viral Vector Core, UMass Chan Medical School, Worcester, MA, USA.
Thomas L GallagherDepartment of Genetics and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.
Zixiu LiDepartment of Population and Quantitative Health Science, UMass Chan Medical School, Worcester, MA, USA.
Chan ZhouDepartment of Population and Quantitative Health Science, UMass Chan Medical School, Worcester, MA, USA.
Phillip W L TaiHorae Gene Therapy Center, UMass Chan Medical School, Worcester, MA, USA; Department of Genetics and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA; Li Weibo Institute for Rare Diseases Research, UMass Chan Medical School, Worcester, MA, USA; Department of Microbiology, UMass Chan Medical School, Worcester, MA, USA.
Guangping GaoHorae Gene Therapy Center, UMass Chan Medical School, Worcester, MA, USA; Viral Vector Core, UMass Chan Medical School, Worcester, MA, USA; Department of Genetics and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA; Li Weibo Institute for Rare Diseases Research, UMass Chan Medical School, Worcester, MA, USA; Department of Microbiology, UMass Chan Medical School, Worcester, MA, USA. Electronic address: guangping.gao@umassmed.edu.
Jun XieHorae Gene Therapy Center, UMass Chan Medical School, Worcester, MA, USA; Viral Vector Core, UMass Chan Medical School, Worcester, MA, USA; Department of Genetics and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA; Li Weibo Institute for Rare Diseases Research, UMass Chan Medical School, Worcester, MA, USA; Department of Microbiology, UMass Chan Medical School, Worcester, MA, USA. Electronic address: jun.xie@umassmed.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Acetaminophen (APAP) overdose is a leading cause of acute liver failure (ALF), primarily through the excessive production of N-acetyl-p-benzoquinone imine (NAPQI). N-acetylcysteine (NAC) is the Food and Drug Administration-approved treatment for APAP overdose, but there is a growing interest in microRNAs as potential therapeutic agents. We delivered miR-375 ectopically via a liver-tropic adeno-associated virus serotype 8 (AAV8) and demonstrated its potent protection in a murine model of APAP overdose-induced ALF. Slc16a2, Cyb5b, and Acsl5 were identified as critical targets acting synergistically to mitigate toxicity. Liver transcriptome revealed that miR-375 overexpression or silencing of the targets of miR-375 increased Gstm3 expression in mice. AAV8-mediated Gstm3 expression protects against APAP-ALF, and the protection was further enhanced by disrupting the expression of Cyp2e1. Additionally, CYP2E1 and GSS, which contribute to APAP detoxification, were down- and upregulated by miR-375, respectively. These findings suggest that miR-375 prevents APAP-ALF by orchestrating the expression of pharmacogenes and enhancing glutathione synthesis. We conclude that miR-375 and its targets are promising therapeutic targets for APAP-ALF.

Indexed as

AcetaminophenChemical and Drug Induced Liver InjuryGene Expression RegulationLiver Failure, AcuteMicroRNAsAnimalsCytochrome P-450 CYP2E1DependovirusDisease Models, AnimalGenetic VectorsGlutathione TransferaseHumansLiverMaleMiceAcetaminophenCytochrome P-450 CYP2E1Glutathione TransferaseMicroRNAsAAVacetaminophenAcsl5acute liver failureCyb5bglutathioneGstm3miR-375Slc16a2

Identifiers

PMID40598772
PMCPMC12848206

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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.