ArticleJCI insight2023
Notch-mediated hepatocyte MCP-1 secretion causes liver fibrosis.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Therapeutic potential of Akkermansia muciniphila in non-alcoholic fatty liver disease: a systematic review.BMC gastroenterology · 2025Pooled it
- Ethanol reshapes FFC-driven steatohepatitis through time-dependent fibrosis and lipid-droplet remodeling.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- An Optimized Freeze-Dry Multimodal Workflow for Sequential Micro-CT Imaging, Histology, and Molecular Profiling: A Use Case in Human Liver Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- TGFβ activity stabilizes ACC1 to increase de novo lipogenesis in metabolic liver disease.Molecular metabolism · 2026Article
- The instructive scar - the dynamic role of extracellular matrix in biliary pathophysiology.Disease models & mechanisms · 2026Review
- Fondaparinux attenuates methotrexate-induced hepatotoxicity by regulating coagulation, endothelial dysfunction, and inflammatory signaling via the TLR4/NLRP3 and NF-κB/IL-1β/MCP-1 pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Enhanced metabolic benefits of dietary methionine restriction in cold resistant hybrid UCP1-deficient mice.The Journal of nutritional biochemistry · 2026Article
- An LSEC-focused computational drug repurposing platform for liver fibrosis: Identification of vorinostat and other LSEC-protective candidates.bioRxiv : the preprint server for biology · 2026Article
- Ultrasound-Assisted Enzymatic Hydrolysates from Common Bean and Pumpkin Seed Proteins: Antioxidant and Anti-Inflammatory Properties.Antioxidants (Basel, Switzerland) · 2026Article
- Chemokines and chemokine receptors in metabolic dysfunction-associated steatohepatitis: pathogenic mechanisms and clinical implications.Cellular & molecular biology letters · 2026Review
- Novel Potential Markers of Metabolic Dysfunction-Associated Steatohepatitis Prone to Hepatocellular Carcinoma.Canadian journal of gastroenterology & hepatology · 2026Article
- Unraveling the pleiotropic effects of CCR2-dependent signal transduction in fibrosis development.Theranostics · 2026Review
- Notch signaling in liver diseases: mechanistic insights and therapeutic implications.Frontiers in cell and developmental biology · 2026Review
- Paeoniflorin Ameliorates Metabolic Dysfunction-Associated Steatotic Liver Disease by SYK/SH3BP2 Signaling Pathway.Research (Washington, D.C.) · 2026Article
- CD209a regulates metabolic dysfunction-associated steatotic liver disease development through macrophage STAT3 signaling pathway.Cellular & molecular biology letters · 2025Article
- Plasma inflammatory proteome profiles identify MASLD among children with overweight or obesity.Cardiovascular diabetology · 2025Article
- Neutrophil extracellular trapping network-associated biomarkers in liver fibrosis: machine learning and experimental validation.Journal of translational medicine · 2025Article
- Obesity-Driven Metabolic Disorders: The Interplay of Inflammation and Mitochondrial Dysfunction.International journal of molecular sciences · 2025Review
- Preventive and Therapeutic Potential of Streptococcus cristatus CA119 in Experimental Periodontitis in Rats.Probiotics and antimicrobial proteins · 2025Article
- The Intriguing Roles of Cytokines in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Narrative Review.Current obesity reports · 2025Review
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 4 countries.
Funding
Abstract
Patients with nonalcoholic steatohepatitis (NASH) have increased expression of liver monocyte chemoattractant protein-1 (MCP-1), but its cellular source and contribution to various aspects of NASH pathophysiology remain debated. We demonstrated increased liver CCL2 (which encodes MCP-1) expression in patients with NASH, and commensurately, a 100-fold increase in hepatocyte Ccl2 expression in a mouse model of NASH, accompanied by increased liver monocyte-derived macrophage (MoMF) infiltrate and liver fibrosis. To test repercussions of increased hepatocyte-derived MCP-1, we generated hepatocyte-specific Ccl2-knockout mice, which showed reduced liver MoMF infiltrate as well as decreased liver fibrosis. Forced hepatocyte MCP-1 expression provoked the opposite phenotype in chow-fed wild-type mice. Consistent with increased hepatocyte Notch signaling in NASH, we observed a close correlation between markers of Notch activation and CCL2 expression in patients with NASH. We found that an evolutionarily conserved Notch/recombination signal binding protein for immunoglobulin kappa J region binding site in the Ccl2 promoter mediated transactivation of the Ccl2 promoter in NASH diet-fed mice. Increased liver MoMF infiltrate and liver fibrosis seen in opposite gain-of-function mice was ameliorated with concomitant hepatocyte Ccl2 knockout or CCR2 inhibitor treatment. Hepatocyte Notch activation prompts MCP-1-dependent increase in liver MoMF infiltration and fibrosis.
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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.