ArticleActa pharmaceutica Sinica. B2021
Dual roles of p62/SQSTM1 in the injury and recovery phases of acetaminophen-induced liver injury in mice.
Article in Acta pharmaceutica Sinica. B, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Loss of Vacuole Membrane Protein 1 protects against acetaminophen-induced liver injury by modulating inflammation and hepatocyte proliferation.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Mouse models to study von Willebrand factor in inflammation: a scoping review.Intensive care medicine experimental · 2026Review
- The SQSTM1/Animals : an open access journal from MDPI · 2026Article
- Understanding Liver and Digestive Diseases: A Paved Road to Improve Diagnosis, Management, and Treatment.Exploration of digestive diseases · 2026Article
- Article
- Amelioration of Acetaminophen-Induced Hepatic Oxidative Stress and Inflammation by RNAi TargetingCurrent issues in molecular biology · 2025Article
- Hepatoprotective Effects of Resveratrol on Acetaminophen-Induced Acute Liver Injury and Its Implications for Tofacitinib Disposition in Rats.Biomolecules & therapeutics · 2025Article
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- Cajaninstilbene Acid and Its Derivative as Multi-Therapeutic Agents: A Comprehensive Review.Molecules (Basel, Switzerland) · 2024Review
- Paeoniflorin protects hepatocytes from APAP-induced damage through launching autophagy via the MAPK/mTOR signaling pathway.Cellular & molecular biology letters · 2024Article
- Article
- The SIRT2-AMPK axis regulates autophagy induced by acute liver failure.Scientific reports · 2024Article
- High-throughput screening of novel TFEB agonists in protecting against acetaminophen-induced liver injury in mice.Acta pharmaceutica Sinica. B · 2024Article
- Natural Products for Acetaminophen-Induced Acute Liver Injury: A Review.Molecules (Basel, Switzerland) · 2023Review
- Article
- The E3 ubiquitin ligase NEDD4-1 protects against acetaminophen-induced liver injury by targeting VDAC1 for degradation.Acta pharmaceutica Sinica. B · 2023Article
- Predatory bacterial hydrogels for topical treatment of infected wounds.Acta pharmaceutica Sinica. B · 2023Article
- Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Acetaminophen (APAP) overdose can induce liver injury and is the most frequent cause of acute liver failure in the United States. We investigated the role of p62/SQSTM1 (referred to as p62) in APAP-induced liver injury (AILI) in mice. We found that the hepatic protein levels of p62 dramatically increased at 24 h after APAP treatment, which was inversely correlated with the hepatic levels of APAP-adducts. APAP also activated mTOR at 24 h, which is associated with increased cell proliferation. In contrast, p62 knockout (KO) mice showed increased hepatic levels of APAP-adducts detected by a specific antibody using Western blot analysis but decreased mTOR activation and cell proliferation with aggravated liver injury at 24 h after APAP treatment. Surprisingly, p62 KO mice recovered from AILI whereas the wild-type mice still sustained liver injury at 48 h. We found increased number of infiltrated macrophages in p62 KO mice that were accompanied with decreased hepatic von Willebrand factor (VWF) and platelet aggregation, which are associated with increased cell proliferation and improved liver injury at 48 h after APAP treatment. Our data indicate that p62 inhibits the late injury phase of AILI by increasing autophagic selective removal of APAP-adducts and mitochondria but impairs the recovery phase of AILI likely by enhancing hepatic blood coagulation.
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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.