Evidence map›Paper›PMID 41366830›Full record

ArticlePhysiological reports2025

Ataxia-telangiectasia mutated activation mediates transforming growth factor beta signaling in acetaminophen-induced liver injury in mice.

Matthew McMillin, Christopher S Chu, Elaina Williams, Juliet Venter, Kiersten Bell, Anca D Petrescu, Patrick Mireles, Sharon DeMorrow

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Physiological reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

8 authors.

Matthew McMillinHuffington Department of Education, Innovation & Technology, Baylor College of Medicine, Temple, Texas, USA.
Christopher S ChuDivision of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas, USA.
Elaina WilliamsDivision of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas, USA.
Juliet VenterDivision of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas, USA.
Kiersten BellDivision of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas, USA.
Anca D PetrescuDivision of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas, USA.
Patrick MirelesDivision of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas, USA.
Sharon DeMorrowDivision of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas, USA.ORCID 0000-0002-0511-9778

Funding

Molecular mechanisms of drug-induced liver injuryR01DK112803 · NIDDK · UNIVERSITY OF TEXAS AT AUSTIN · PI DEMORROW, SHARON · 2018 to 2021
$1.4M
HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) DK112803HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) DK135995NIDDK NIH HHS R01 DK112803
6 · The paper itself

Abstract

Acetaminophen (APAP) overdose is associated with increased transforming growth factor beta 1 (TGFβ1) signaling and elevated oxidative stress, which exacerbate DNA damage. TGFβ1 has been shown to regulate ataxia-telangiectasia mutated (ATM) signaling and DNA repair in other cell types. This study investigates the DNA damage response (DDR) during APAP-induced liver injury, focusing on ATM-mediated regulation of TGFβ1 signaling. APAP administration in vitro and in vivo resulted in DNA damage, increased ATM signaling, accumulation of γH2AX, and activation of phosphorylated ataxia telangiectasia mutated (pATM) and phosphorylated checkpoint kinase 2 (pChk2). Pretreatment with an ATM inhibitor, KU55933, attenuated APAP-induced hepatocyte damage and resulted in attenuated mothers against decapentaplegic homolog 2/3 (SMAD2/3) signaling with no changes in activated TGFβ1 levels, suggesting that ATM activation modulates TGFβ1 signaling via post-translational mechanisms. APAP was found to promote transforming growth factor beta receptor 2 (TGFβRII) stabilization through activation of phosphorylated casitas B-lineage lymphoma (p-c-cbl) and subsequent neddylation of TGFβRII, which was attenuated by inhibitors of ATM signaling or neddylation machinery. In conclusion, APAP-induced hepatic DNA damage activates an ATM-mediated response that enhances TGFβ1 signaling through stabilization of TGFβRII, and inhibition of ATM consequently reduces APAP-induced hepatic injury.

Indexed as

AcetaminophenAtaxia Telangiectasia Mutated ProteinsChemical and Drug Induced Liver InjuryTransforming Growth Factor beta1AnimalsDNA DamageHepatocytesMaleMiceMice, Inbred C57BLSignal TransductionAcetaminophenAtaxia Telangiectasia Mutated ProteinsAtm protein, mouseTransforming Growth Factor beta1acute liver injuryDNA damageDNA damage responseKU55933SMAD signaling

Identifiers

PMID41366830
PMCPMC12689461

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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.