ArticleCell2018
ER Stress Drives Lipogenesis and Steatohepatitis via Caspase-2 Activation of S1P.
Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 192 papers.
What it found
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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.
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Who cites it
192 citing papers in PubMed, 335 citations in OpenAlex.
- S100A11 regulates hepatic cholesterol metabolism and promotes steatohepatitis via noncanonical SREBP2 signaling.The Journal of clinical investigation · 2026Article
- Molecular mechanisms and pathogenesis of MASH.Nature · 2026Review
- Gut microbiota-derived indole-3-propionic acid alleviates endoplasmic reticulum stress by regulating FMO2 in MASLD.Hepatology communications · 2026Article
- Deficiency of PTEN Confers Hypersensitivity to Fatty Acid-Mediated ER Stress in Transformed Hepatocytes.International journal of molecular sciences · 2026Article
- Dysregulation of the AMPK-SREBP1-FASN axis in MASLD: driving a vicious cycle of lipotoxicity and metabolic-immune crosstalk.Lipids in health and disease · 2026Review
- Cartilage Intermediate Layer Protein 2 Aggravates Hepatic Lipid Accumulation and Inflammation Through the IRE1α/XBP1 Pathway.International journal of molecular sciences · 2026Article
- Caspase-2 deficiency drives pathogenic liver polyploidy and increases age-associated hepatocellular carcinoma in mice.Science advances · 2026Article
- Cell membrane-coated nanoparticles against non-alcoholic fatty liver disease via regulating endoplasmic reticulum stress.Regenerative biomaterials · 2026Article
- Fermented Milk as an Alternative Therapy for Obesity.International journal of food science · 2026Review
- The role of the transcription factor KLF16 in metabolic dysfunction associated fatty liver disease: regulatory linkages between lipid deposition and the expression of ATF4.Annals of medicine · 2025Article
- Mesenchymal stem cell-derived exosomes as cell-free therapeutics: mechanistic insights and engineering strategies for liver disease treatment.Stem cell research & therapy · 2025Review
- Combination of THU/ALK-5i exhibits profound anti-MASH activity through suppression of lipogenesis and fibrogenesis.Scientific reports · 2025Article
- Endoplasmic reticulum stress at the forefront of fatty liver diseases and cancer.Pharmacological reviews · 2025Review
- Taurine alleviates endoplasmic reticulum stress, oxidative stress, apoptosis, and glycogen accumulation induced by high glucose in the muscle cells of golden pompano (Marine life science & technology · 2025Article
- Chronic hypoxia induces liver injury via PKCδ/ASMase-driven ceramide accumulation and endoplasmic reticulum stress in rats.Lipids in health and disease · 2025Article
- Regulation of Hepatic Stellate Cell Phenotypes in Metabolic Dysfunction-Associated Steatohepatitis.Gastroenterology · 2025Review
- Article
- Site-1 protease is a negative regulator of sarcolipin promoter activity.Communications biology · 2025Article
- Hepatic Insulin Resistance and Steatosis in Metabolic Dysfunction-Associated Steatotic Liver Disease: New Insights into Mechanisms and Clinical Implications.Diabetes & metabolism journal · 2025Review
- MBTPS1: a membrane-bound transcription factor protease implicated in the pathogenesis of several skin and skeletal disorders.Functional & integrative genomics · 2025Review
132 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
9 authors at 2 institutions in 1 country.
Funding
Abstract
Nonalcoholic fatty liver disease (NAFLD) progresses to nonalcoholic steatohepatitis (NASH) in response to elevated endoplasmic reticulum (ER) stress. Whereas the onset of simple steatosis requires elevated de novo lipogenesis, progression to NASH is triggered by accumulation of hepatocyte-free cholesterol. We now show that caspase-2, whose expression is ER-stress inducible and elevated in human and mouse NASH, controls the buildup of hepatic-free cholesterol and triglycerides by activating sterol regulatory element-binding proteins (SREBP) in a manner refractory to feedback inhibition. Caspase-2 colocalizes with site 1 protease (S1P) and cleaves it to generate a soluble active fragment that initiates SCAP-independent SREBP1/2 activation in the ER. Caspase-2 ablation or pharmacological inhibition prevents diet-induced steatosis and NASH progression in ER-stress-prone mice. Caspase-2 inhibition offers a specific and effective strategy for preventing or treating stress-driven fatty liver diseases, whereas caspase-2-generated S1P proteolytic fragments, which enter the secretory pathway, are potential NASH biomarkers.
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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.