ArticleGut2021
Sphingomyelin synthase 1 mediates hepatocyte pyroptosis to trigger non-alcoholic steatohepatitis.
Article in Gut, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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.
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.
Who cites it
88 citing papers in PubMed, 151 citations in OpenAlex.
- The convergent roles of metabolic dysfunction, alcohol, and iron in steatotic liver disease: a review.Bioscience reports · 2026Review
- Periodontitis aggravates high-fat diet-induced MASLD via gut microbiota dysbiosis and metabolic dysfunction in mice.Scientific reports · 2026Article
- Mechanisms and reversal strategies of liver fibrosis: from regulation of cell fate to clinical translation.Journal of translational medicine · 2026Review
- Regulated necrosis at the crossroads of liver inflammation and cancer development.Nature reviews. Gastroenterology & hepatology · 2026Review
- Sex-based multiomics analysis uncovers metabolic and molecular mediators linking MASH and atherosclerosis.JHEP reports : innovation in hepatology · 2026Article
- β-sitosterol attenuates hepatic lipid accumulation and fibrosis via NLRP3 signaling in MASH mice.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- The Role of Kupffer Cells and Liver Macrophages in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease.Biomedicines · 2026Review
- Calcium imbalance drives organelle network collapse and immune remodeling: novel pathogenic mechanisms in MASLD progression.Frontiers in immunology · 2026Review
- Exploring potential associations between blood metabolites and cirrhosis risk: a Mendelian randomization and LC-MS/MS analysis.Frontiers in medicine · 2026Article
- Tao-Hong-Si-Wu-Tang protects against methionine- and choline-deficient diet-induced hepatic steatosis in rats and is associated with inhibition of oxidative stress, inflammation, apoptosis, and pyroptosis.Frontiers in immunology · 2026Article
- Lipid metabolism-MAFLD crosstalk: mechanisms and therapy.Frontiers in endocrinology · 2026Review
- Loss of LCAT function aggravates metabolic-associated steatohepatitis (MASH) in golden Syrian hamster.Clinical science (London, England : 1979) · 2025Article
- Involvement of ferroptosis in metabolic dysfunction-associated steatohepatitis-related liver diseases.Journal of molecular medicine (Berlin, Germany) · 2025Review
- MASH: the nexus of metabolism, inflammation, and fibrosis.The Journal of clinical investigation · 2025Review
- Killing hepatocellular carcinoma in the NAFLD/NASH stage: a comprehensive perspective on targeting regulated cell death.Cell death discovery · 2025Review
- Identification of pyroptosis-associated gene to predict fibrosis and reveal immune characterization in non-alcoholic fatty liver disease.Scientific reports · 2025Article
- GSDMD-mediated pyroptosis: molecular mechanisms, diseases and therapeutic targets.Molecular biomedicine · 2025Review
- Therapeutic Targets and Approaches to Manage Inflammation of NAFLD.Biomedicines · 2025Review
- MASH as an emerging cause of hepatocellular carcinoma: current knowledge and future perspectives.Molecular oncology · 2025Review
- Relationship between Abnormal Lipid Metabolism and Gallstone Formation.The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi · 2025Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 6 institutions in 3 countries.
Funding
Abstract
objectiveLipotoxic hepatocyte injury is a primary event in non-alcoholic steatohepatitis (NASH), but the mechanisms of lipotoxicity are not fully defined. Sphingolipids and free cholesterol (FC) mediate hepatocyte injury, but their link in NASH has not been explored. We examined the role of free cholesterol and sphingomyelin synthases (SMSs) that generate sphingomyelin (SM) and diacylglycerol (DAG) in hepatocyte pyroptosis, a specific form of programmed cell death associated with inflammasome activation, and NASH.
designWild-type C57BL/6J mice were fed a high fat and high cholesterol diet (HFHCD) to induce NASH. Hepatic SMS1 and SMS2 expressions were examined in various mouse models including HFHCD-fed mice and patients with NASH. Pyroptosis was estimated by the generation of the gasdermin-D N-terminal fragment. NASH susceptibility and pyroptosis were examined following knockdown of SMS1, protein kinase Cδ (PKCδ), or the NLR family CARD domain-containing protein 4 (NLRC4).
resultsHFHCD increased the hepatic levels of SM and DAG while decreasing the level of phosphatidylcholine. Hepatic expression of
conclusionSMS1 mediates hepatocyte pyroptosis through a novel DAG-PKCδ-NLRC4 axis and holds promise as a therapeutic target for NASH.
Indexed as
Identifiers
What OpenQuestion holds
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.