ArticleToxicological sciences : an official journal of the Society of Toxicology2017
Dual Role of Epidermal Growth Factor Receptor in Liver Injury and Regeneration after Acetaminophen Overdose in Mice.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 68 citations in OpenAlex.
- Viburnum opulus protects against acetaminophen-induced splenic injury through coordinated antioxidant and anti-inflammatory responses.Journal of molecular histology · 2026Article
- The pivotal role of mitochondria in the pathogenesis and treatment of liver failure: a comprehensive review.Molecular and cellular biochemistry · 2026Review
- 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
- Two types of regenerative cell populations appear in acute liver injury.Stem cell reports · 2025Article
- EGF receptor in organ development, tissue homeostasis and regeneration.Journal of biomedical science · 2025Review
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- Potential role of epidermal growth factor receptors (EGFR) signaling in the pathogenesis and management of hepatocellular carcinoma.BioImpacts : BI · 2025Review
- Myeloid derived suppressor cells mediate hepatocyte proliferation and immune suppression during liver regeneration following resection.Genes and immunity · 2024Article
- IGFBP2 functions as an endogenous protector against hepatic steatosis via suppression of the EGFR-STAT3 pathway.Molecular metabolism · 2024Article
- The Role of Mechanistic Biomarkers in Understanding Acetaminophen Hepatotoxicity in Humans.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- The state of the art in secondary pharmacology and its impact on the safety of new medicines.Nature reviews. Drug discovery · 2024Review
- The thrombopoietin mimetic JNJ-26366821 reduces the late injury and accelerates the onset of liver recovery after acetaminophen-induced liver injury in mice.Archives of toxicology · 2024Article
- Acetaminophen Hepatotoxicity: Paradigm for Understanding Mechanisms of Drug-Induced Liver Injury.Annual review of pathology · 2024Review
- EGR1 is crucial for the chlorogenic acid-provided promotion on liver regeneration and repair after APAP-induced liver injury.Cell biology and toxicology · 2023Article
- Article
- EGF-receptor phosphorylation and downstream signaling are activated by genistein during subacute liver damage.Journal of molecular histology · 2023Article
- Effect of Hepatic Pathology on Liver Regeneration: The Main Metabolic Mechanisms Causing Impaired Hepatic Regeneration.International journal of molecular sciences · 2023Review
- New Insight Into Mechanisms of Hepatic Encephalopathy: An Integrative Analysis Approach to Identify Molecular Markers and Therapeutic Targets.Bioinformatics and biology insights · 2023Article
- The immunological mechanisms and therapeutic potential in drug-induced liver injury: lessons learned from acetaminophen hepatotoxicity.Cell & bioscience · 2022Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Epidermal growth factor receptor (EGFR) plays a crucial role in hepatocyte proliferation. Its role in acetaminophen (APAP)-mediated hepatotoxicity and subsequent liver regeneration is completely unknown. Role of EGFR after APAP-overdose in mice was studied using pharmacological inhibition strategy. Rapid, sustained and dose-dependent activation of EGFR was noted after APAP-treatment in mice, which was triggered by glutathione depletion. EGFR-activation was also observed in primary human hepatocytes after APAP-treatment, preceding elevation of toxicity markers. Treatment of mice with an EGFR-inhibitor (EGFRi), Canertinib, 1h post-APAP resulted in robust inhibition of EGFR-activation and a striking reduction in APAP-induced liver injury. Metabolic activation of APAP, formation of APAP-protein adducts, APAP-mediated JNK-activation and its mitochondrial translocation were not altered by EGFRi. Interestingly, EGFR rapidly translocated to mitochondria after APAP-treatment. EGFRi-treatment abolished mitochondrial EGFR activity, prevented APAP-mediated mitochondrial dysfunction/oxidative-stress and release of endonucleases from mitochondria, which are responsible for DNA-damage/necrosis. Treatment with N-acetylcysteine (NAC), 4h post-APAP in mice did not show any protection but treatment of EGFRi in combination with NAC showed decrease in liver injury. Finally, delayed treatment with EGFRi, 12-h post-APAP, did not alter peak injury but caused impairment of liver regeneration resulting in sustained injury and decreased survival after APAP overdose in mice. Impairment of regeneration was due to inhibition of cyclinD1 induction and cell cycle arrest. Our study has revealed a new dual role of EGFR both in initiation of APAP-injury and in stimulation of subsequent compensatory regeneration after APAP-overdose.
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Registered trials
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.