ArticleScience translational medicine2018
Hepatocyte Notch activation induces liver fibrosis in nonalcoholic steatohepatitis.
Article in Science translational medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 162 papers.
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Who cites it
162 citing papers in PubMed, 241 citations in OpenAlex.
- A refined MASH-HCC model identifies macrophage Gadd45b as a key orchestrator of inflammation-driven neoplastic progression.Experimental & molecular medicine · 2026Article
- The Emerging Challenge of Non-Cirrhotic MASLD-Related Hepatocellular Carcinoma: Etiology, Immunopathology, and Precision Oncology.Liver cancer · 2026Review
- TGFβ activity stabilizes ACC1 to increase de novo lipogenesis in metabolic liver disease.Molecular metabolism · 2026Article
- Hepatocyte CD146 and soluble CD146 promote hepatic stellate cell activation via the integrin αvβ1-p38 MAPK signaling axis to drive liver fibrosis.Cellular and molecular life sciences : CMLS · 2026Article
- Mitochondrial Dysfunction in Metabolic-Syndrome-Related MASLD/MASH: Metabolic Mechanisms and Therapeutic Perspectives.Metabolites · 2026Review
- Therapeutic targeting of AREL1 in hepatic stellate cells attenuates MASH-related liver fibrosis.Nature communications · 2026Article
- P-STAT3-dependent SPP1 transcription in cholangiocytes drives hepatic stellate cells activation in congenital hepatic fibrosis.Communications biology · 2026Article
- Mechanisms and reversal strategies of liver fibrosis: from regulation of cell fate to clinical translation.Journal of translational medicine · 2026Review
- Altered Bile Acid Transport in Liver Disease.Biomedicines · 2026Review
- A Gut-Restricted Liver X Receptor Agonist Ameliorates Liver Injury in Experimental Short Bowel Syndrome.Gastroenterology · 2026Article
- Redefining senescence through hepatocyte fate changes in liver diseases.Trends in endocrinology and metabolism: TEM · 2026Review
- Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Hepatocyte TonEBP promotes metabolic stress-induced hepatic fibroinflammation involving transcriptional activation of ELR⁺ CXC chemokines.Cell death discovery · 2026Article
- Complex I Modulator BI4500 Reduces MASH by Limiting Oxidative Stress and Reprogramming Lipid Metabolism via AMPK in MCD Rats.Antioxidants (Basel, Switzerland) · 2026Article
- Neutrophil extracellular traps-triggered hepatocellular senescence exacerbates lipotoxicity in non-alcoholic steatohepatitis.Journal of advanced research · 2026Article
- Extracellular matrix stiffness in hepatocellular carcinoma: mechanisms and targeted therapeutic strategies.Frontiers in immunology · 2026Review
- Dysfunctional macrophages along the gut-liver axis: a driver of infection in cirrhosis.Frontiers in immunology · 2026Review
- Notch signaling in liver diseases: mechanistic insights and therapeutic implications.Frontiers in cell and developmental biology · 2026Review
- Investigating epigenetic biomarkers of age, sex, and disease in captive South African cheetahs (Acinonyx jubatus jubatus).PloS one · 2026Article
- Immune crosstalk in metabolic dysfunction-associated steatotic liver disease: interactions between innate and adaptive immunity.Frontiers in immunology · 2026Review
102 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
Fibrosis is the major determinant of morbidity and mortality in patients with nonalcoholic steatohepatitis (NASH) but has no approved pharmacotherapy in part because of incomplete understanding of its pathogenic mechanisms. Here, we report that hepatocyte Notch activity tracks with disease severity and treatment response in patients with NASH and is similarly increased in a mouse model of diet-induced NASH and liver fibrosis. Hepatocyte-specific Notch loss-of-function mouse models showed attenuated NASH-associated liver fibrosis, demonstrating causality to obesity-induced liver pathology. Conversely, forced activation of hepatocyte Notch induced fibrosis in both chow- and NASH diet-fed mice by increasing Sox9-dependent Osteopontin (Opn) expression and secretion from hepatocytes, which activate resident hepatic stellate cells. In a cross-sectional study, we found that OPN explains the positive correlation between liver Notch activity and fibrosis stage in patients. Further, we developed a Notch inhibitor [
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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.