ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
OPN-Mediated Crosstalk Between Hepatocyte E4BP4 and Hepatic Stellate Cells Promotes MASH-Associated Liver Fibrosis.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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The trial behind it
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Who cites it
16 citing papers in PubMed.
- E4BP4 interacts with PERK to form a feedback loop mediating cold-induced female reproductive disorders.Cell stress & chaperones · 2026Article
- Therapeutic targeting of AREL1 in hepatic stellate cells attenuates MASH-related liver fibrosis.Nature communications · 2026Article
- When the Liver Flares: Inflammatory and Immunometabolic Mechanisms Driving the Transition from MASLD to MASH.Inflammation · 2026Review
- NUP85 Mediates Endoplasmic Reticulum Stress through the USP47/ASK1 Signaling Pathway to Regulate the Progression of Liver Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrated transcriptomic analysis identifies liver aging-driven fibrosis signatures and reveals therapeutic strategies based on medicine-food homology.NPJ science of food · 2026Article
- Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- 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
- Calcium imbalance drives organelle network collapse and immune remodeling: novel pathogenic mechanisms in MASLD progression.Frontiers in immunology · 2026Review
- Osteopontin: a central hub in the pathogenesis and therapeutic intervention of liver disease.Annals of medicine · 2025Review
- Identification of CTSK as a TLR-related critical biomarker in liver cirrhosis via integrative bioinformatics and pathological characterization.Scientific reports · 2025Article
- Osteopontin in Chronic Inflammatory Diseases: Mechanisms, Biomarker Potential, and Therapeutic Strategies.Biology · 2025Review
- TRAF2 Promotes Liver Fibrosis via Regulation of the HIF-1α/GLUT1-Mediated Glycolysis in Hepatic Stellate Cells.International journal of biological sciences · 2025Article
- Dynamic crosstalk between HSCs and liver microenvironment: multicellular interactions in the regulation of liver fibrosis.Frontiers in cell and developmental biology · 2025Review
- Steatotic liver disease and cancer: from pathogenesis to therapeutic targets.eGastroenterology · 2025Review
- OPN-Mediated Crosstalk Between Hepatocyte E4BP4 and Hepatic Stellate Cells Promotes MASH-Associated Liver Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Inter-organ metabolic interaction networks in non-alcoholic fatty liver disease.Frontiers in endocrinology · 2024Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Stressed hepatocytes promote liver fibrosis through communications with hepatic stellate cells (HSCs) during chronic liver injury. However, intra-hepatocyte players that facilitate such cell-to-cell communications are largely undefined. It is previously reported that hepatocyte E4BP4 is potently induced by ER stress and hepatocyte deletion of E4bp4 protects mice from high-fat diet-induced liver steatosis. Here how hepatocyte E4bp4 deficiency impacts the activation of HSCs and the progression toward MASH-associated liver fibrosis is examined. Hepatic E4BP4 is increased in mouse models of NASH diet- or CCl4-induced liver fibrosis. Hepatocyte-specific E4bp4 deletion protected mice against NASH diet-induced liver injury, inflammation, and fibrosis without impacting liver steatosis. Hepatocyte E4BP4 overexpression activated HSCs in a medium transfer experiment, whereas hepatocyte E4bp4 depletion did the opposite. RNA-Seq analysis identified the pro-fibrogenic factor OPN as a critical target of E4BP4 within hepatocytes. Antibody neutralization or shRNA depletion of Opn abrogated hepatocyte E4BP4-induced HSC activation. E4BP4 interacted with and stabilized YAP, an established activator of OPN. Loss of hepatic Yap blocked OPN induction in the liver of Ad-E4bp4-injected mice. Hepatocyte E4BP4 induces OPN via YAP to activate HSCs and promote liver fibrosis during diet-induced MASH. Inhibition of the hepatocyte E4BP4-OPN pathway could offer a novel therapeutic avenue for treating MASLD/MASH.
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