ArticleJournal of hepatology2021
Hepatocyte pyroptosis and release of inflammasome particles induce stellate cell activation and liver fibrosis.
Article in Journal of hepatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 304 papers.
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Who cites it
304 citing papers in PubMed, 520 citations in OpenAlex.
- Clinical efficacy of Radix Arnebiae oil in patients undergoing incision and drainage of perianal abscess and its effects on pyroptosis.Frontiers in cellular and infection microbiology · 2026Trial
- Fumarate and Its Esters: Physiology, Pathology, Molecular Mechanisms, Diseases, and Therapy.MedComm · 2026Review
- Nifuroxazide Pretreatment Protects Against Acute CdClAntioxidants (Basel, Switzerland) · 2026Article
- Elucidating the beneficial effects of gut microbiota-derived metabolites in treating hepatocellular carcinoma: an integrated network pharmacology, molecular docking, and single-cell sequencing analysis.Bioresources and bioprocessing · 2026Article
- Natural Small Molecules Targeting Mitochondrial Quality Control for the Treatment of Metabolic Diseases: Mechanisms, Novel Formulations, and Translational Perspectives.Pharmaceuticals (Basel, Switzerland) · 2026Review
- The NLRP3 inflammasome as a dynamic context-dependent regulator: mechanisms, disease progression, and therapeutic implications.Journal of translational medicine · 2026Review
- Targeting FAPActa pharmaceutica Sinica. B · 2026Article
- Rutin attenuates liver fibrosis via the IRG1-itaconate-Nrf2 axis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- USP9X regulates copper-induced CASP9/CASP3/GSDME-dependent pyroptosis by deubiquitinating JAK1.Apoptosis : an international journal on programmed cell death · 2026Article
- Gut microenvironment-responsive copper selenide/disulfiram/eudragitJournal of nanobiotechnology · 2026Article
- Lacticaseibacillus paracasei 36 attenuates D-GalN/LPS-induced acute liver injury in mice via suppressing the TLR4/NF-κB/MAPK pathway and NLRP3 inflammasome activation through modulating the intestinal microbiota.Journal of advanced research · 2026Article
- Altered Properties of Bone Marrow-Derived Mesenchymal Stem Cells Exposed to Serum from Patients with Acute-On-Chronic Liver Failure.International journal of stem cells · 2026Article
- Disulfidptosis in hepatocellular carcinoma: molecular mechanisms, therapeutic potential, and exploratory insights into chronic liver diseases.Apoptosis : an international journal on programmed cell death · 2026Review
- Targeting pyroptosis in metabolic dysfunction-associated steatotic liver disease: from molecular mechanisms to therapeutic innovation.Molecular biology reports · 2026Review
- Advances in understanding mitophagy's role in lung injury.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2026Review
- Fibroblast growth factor 10 attenuates advanced liver fibrosis through hepatocyte fibroblast growth factor receptor 2 signalling.Clinical and translational medicine · 2026Article
- Regulated necrosis at the crossroads of liver inflammation and cancer development.Nature reviews. Gastroenterology & hepatology · 2026Review
- Gut Microbiota Dysbiosis and LPS/NLRP3/GSDMD Pyroptosis Drive Hepatic Fibrosis: Therapeutic Potential of a Synbiotic Intervention.Probiotics and antimicrobial proteins · 2026Article
- Cannabinoid type 2 receptor regulates skeletal muscle regeneration by NLRP3-GSDMD mediated macrophage pyroptosis after injury.Cell death discovery · 2026Article
- 4-phenylbutyric acid attenuates hepatic ER stress, pyroptosis, and NAFLD in adult rat offspring exposed to a high-fat, high-fructose diet during perinatal and adulthood.Lipids in health and disease · 2026Article
244 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 10 institutions in 5 countries.
Funding
Abstract
BACKGROUND &
aimsIncreased hepatocyte death contributes to the pathology of acute and chronic liver diseases. However, the role of hepatocyte pyroptosis and extracellular inflammasome release in liver disease is unknown.
methodsWe used primary mouse and human hepatocytes, hepatocyte-specific leucine 351 to proline Nlrp3
resultsWe demonstrated that primary mouse and human hepatocytes can undergo pyroptosis upon NLRP3 inflammasome activation with subsequent release of NLRP3 inflammasome proteins that amplify and perpetuate inflammasome-driven fibrogenesis. Pyroptosis was inhibited by blocking caspase-1 and gasdermin D activation. The activated form of caspase-1 was detected in the livers and in serum from patients with non-alcoholic steatohepatitis and correlated with disease severity. Nlrp3
conclusionsThese results identify hepatocyte pyroptosis and release of inflammasome components as a novel mechanism to propagate liver injury and liver fibrosis development. LAY SUMMARY: Our findings identify a novel mechanism of inflammation in the liver. Experiments in cell cultures, mice, and human samples show that a specific form of cell death, called pyroptosis, leads to the release of complex inflammatory particles, the NLRP3 inflammasome, from inside hepatocytes into the extracellular space. From there they are taken up by other cells and thereby mediate inflammatory and pro-fibrogenic stress signals. The discovery of this mechanism may lead to novel treatments for chronic liver diseases in the future.
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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.