ArticleThe American journal of pathology2014
Pro-regenerative signaling after acetaminophen-induced acute liver injury in mice identified using a novel incremental dose model.
Article in The American journal of pathology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers.
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Who cites it
127 citing papers in PubMed, 207 citations in OpenAlex.
- Article
- Tissue-based detection of macrophage-associated YAP1-positive material in human acute liver injury: an exploratory immunopathological biopsy series.Diagnostic pathology · 2026Article
- Redefining senescence through hepatocyte fate changes in liver diseases.Trends in endocrinology and metabolism: TEM · 2026Review
- A spatially localised cryoinjury protocol to study liver regeneration in zebrafish.STAR protocols · 2026Article
- Red Deer (Life (Basel, Switzerland) · 2026Article
- Imaging bioactive lipid isomers in acetaminophen-induced liver injury using nano-DESI tandem MS.Journal of lipid research · 2026Article
- Diploid hepatocytes resist acetaminophen-induced liver injury through suppressed JNK signaling.Cell death & disease · 2026Article
- Differential effects on acetaminophen-induced nephrotoxicity and liver injury following modulation of glutathione resynthesis.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2026Article
- Hepatocyte-Specific MET Deletion Exacerbates Acetaminophen-Induced Hepatotoxicity in Mice.The American journal of pathology · 2026Article
- Hepatocyte-specific epidermal growth factor receptor (EGFR) deletion attenuates acetaminophen-induced liver injury in mice.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Widely Targeted Liver Metabolomics Reveals Potential Biomarkers in Mice with Drug-Induced Liver Injury.Metabolites · 2026Article
- Multiscale zonation-resolved modeling of dose-dependent determinants of acetaminophen-induced liver injury.Frontiers in pharmacology · 2026Article
- Non-invasive identification of brain signatures of acute liver injury.Theranostics · 2026Article
- Platelets mediate neutrophil infiltration and exacerbate liver injury and sinusoidal endothelial cell damage after a severe acetaminophen overdose in mice.Archives of toxicology · 2025Article
- A spatially localised cryoinjury model to study liver regeneration in zebrafish.bioRxiv : the preprint server for biology · 2025Article
- A Single Early-Life Acetaminophen Exposure Causes Persistent Abnormalities in the Murine Lung.American journal of respiratory cell and molecular biology · 2025Article
- Comparison of phenotypic and transcriptomic profiles between HFPO-DA and prototypical PPARα, PPARγ, and cytotoxic agents in wild-type and Ppara-null mouse livers.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Kupffer cell expression of macrophage receptor with collagenous structure modulates macrophage gene induction and limits acute liver injury.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Role of mitogens in normal and pathological liver regeneration.Hepatology communications · 2025Review
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
67 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Acetaminophen (APAP) overdose results in acute liver failure and has limited treatment options. Previous studies show that stimulating liver regeneration is critical for survival after APAP overdose, but the mechanisms remain unclear. In this study, we identified major signaling pathways involved in liver regeneration after APAP-induced acute liver injury using a novel incremental dose model. Liver injury and regeneration were studied in C57BL/6 mice treated with either 300 mg/kg (APAP300) or 600 mg/kg (APAP600) APAP. Mice treated with APAP300 developed extensive liver injury and robust liver regeneration. In contrast, APAP600-treated mice exhibited significant liver injury but substantial inhibition of liver regeneration, resulting in sustained injury and decreased survival. The inhibition of liver regeneration in the APAP600 group was associated with cell cycle arrest and decreased cyclin D1 expression. Several known regenerative pathways, including the IL-6/STAT-3 and epidermal growth factor receptor/c-Met/mitogen-activated protein kinase pathways, were activated, even at APAP600, where regeneration was inhibited. However, canonical Wnt/β-catenin and NF-κB pathways were activated only in APAP300-treated mice, where liver regeneration was stimulated. Furthermore, overexpression of a stable form of β-catenin, where serine 45 is mutated to aspartic acid, in mice resulted in improved liver regeneration after APAP overdose. Taken together, our incremental dose model has identified a differential role of several signaling pathways in liver regeneration after APAP overdose and highlighted canonical Wnt signaling as a potential target for regenerative therapies for APAP-induced acute liver failure.
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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.