Evidence map›Paper›PMID 39701936›Full record

ArticleMolecular medicine (Cambridge, Mass.)2024

Depressed TFAM promotes acetaminophen-induced hepatotoxicity regulated by DDX3X-PGC1α-NRF2 signaling pathway.

Sisi Chen, Yaling Cao, Zihao Fan, Ling Xu, Zhenzhen Pan, Yao Gao, Linlin Wei, Qiaoxin Wei, Yuan Tian, Xiangying Zhang and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular medicine (Cambridge, Mass.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
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

12 authors.

Sisi Chen *Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, No. 8, XitouTiao Road, Youwai Street, Fengtai District, Beijing, 100069, China.
Yaling Cao *Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, No. 8, XitouTiao Road, Youwai Street, Fengtai District, Beijing, 100069, China.
Zihao Fan *Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, No. 8, XitouTiao Road, Youwai Street, Fengtai District, Beijing, 100069, China.
Ling XuBeijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, No. 8, XitouTiao Road, Youwai Street, Fengtai District, Beijing, 100069, China.
Zhenzhen PanBeijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, No. 8, XitouTiao Road, Youwai Street, Fengtai District, Beijing, 100069, China.
Yao GaoBeijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, No. 8, XitouTiao Road, Youwai Street, Fengtai District, Beijing, 100069, China.
Linlin WeiThe Second Department of Liver Disease Center, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China.
Qiaoxin WeiBeijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, No. 8, XitouTiao Road, Youwai Street, Fengtai District, Beijing, 100069, China.
Yuan TianBeijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, No. 8, XitouTiao Road, Youwai Street, Fengtai District, Beijing, 100069, China.
Xiangying ZhangBeijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, No. 8, XitouTiao Road, Youwai Street, Fengtai District, Beijing, 100069, China.
Mei LiuDepartment of Liver Oncology, Beijing Youan Hospital, Capital Medical University, No. 8, Xitou Tiao Road, Youwai Street, Fengtai District, Beijing, 100069, China. liumei@ccmu.edu.cn.
Feng RenBeijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, No. 8, XitouTiao Road, Youwai Street, Fengtai District, Beijing, 100069, China. renfeng7512@ccmu.edu.cn.

Funding

2022 Chronic disease prevention and health education research project BJMB0012022028021Beijing Hospitals Authority Youth Programme QML20201702Beijing Municipal Administration of Hospitals Incubating Program PX2021065Beijing Natural Science Foundation-Changping Innovation Joint Fund L234046Beijing You'an Hospital Construction of Talent Pool Program YARCKB2022008Chinese Institutes for Medical Research CX24PY23High-level public health technical personnel construction Project Subject leaders-02-13Key Projects of the Beijing Municipal Education Commission's Science and Technology Plan KZ202010025035National Natural Science Foundation of China 82002243, 82100653Talent Cultivation plan of "Climbing the peak" of Beijing Municipal Hospital Administration DFL20221503Training Fund for Open Projects at Clinical Institutes and Departments of Capital Medical University CCMU2023ZKYXZ003
6 · The paper itself

Abstract

backgroundAcetaminophen (APAP)-induced acute liver injury (AILI) is the most prevalent cause of acute liver failure and mitochondrial dysfunction plays a dominant role in the pathogenesis of AILI. Mitochondrial transcription factor A (TFAM) is an important marker for maintaining mitochondrial functional homeostasis, but its functions in AILI are unclear. This study aimed to investigate the function of TFAM and its regulatory molecular mechanism in the progression of AILI.

methodsThe roles of TFAM and DEAD (Asp-Glu-Ala-Asp) box polypeptide 3 X-linked (DDX3X) in AILI were determined with TFAM overexpression and DDX3X knockdown, respectively.

resultsTFAM expression was suppressed in AILI patients. TFAM overexpression alleviated liver necrosis and mitochondrial dysfunction. Treatment of the AILI mice model with N-acetylcysteine (NAC), a drug used to treat APAP overdose, resulted in significant TFAM activation. In vivo experiments confirmed that TFAM expression was negatively regulated by DDX3X. Mechanistic studies showed that nuclear respiratory factor 2 (NRF-2), a key regulator of TFAM, was selectively activated after DDX3X knockdown via activated peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1α), in vivo and in vitro.

conclusionsThis study demonstrates that depressed hepatic TFAM plays a key role in the pathogenesis of AILI, which is regulated by the DDX3X-PGC1α-NRF2 signaling pathway.

Indexed as

AcetaminophenChemical and Drug Induced Liver InjuryDEAD-box RNA HelicasesDNA-Binding ProteinsMitochondrial ProteinsNF-E2-Related Factor 2Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaSignal TransductionTranscription FactorsAnimalsDisease Models, AnimalFemaleGene Expression RegulationHigh Mobility Group ProteinsHumansMaleAcetaminophenDDX3X protein, humanDEAD-box RNA HelicasesDNA-Binding ProteinsHigh Mobility Group ProteinsMitochondrial ProteinsNF-E2-Related Factor 2Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPPARGC1A protein, humanTFAM protein, humanTfam protein, mouseTranscription FactorsAcetaminophenAcute liver injuryMitochondrial transcription factor APeroxisome proliferator-activated receptor γ-coactivator-1αRespiratory factor 2

Identifiers

PMID39701936
PMCPMC11657569

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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.