ArticleExperimental & molecular medicine2017
Hepatocyte toll-like receptor 4 mediates lipopolysaccharide-induced hepcidin expression.
Article in Experimental & molecular medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 65 citations in OpenAlex.
- Safety and Efficacy of HexaBody-DR5/DR5 in Malignant Solid Tumors: Phase 1/2a Results and Translational Insights Into Observed Hepatotoxicity.Clinical and translational science · 2026Trial
- Inflammatory gut-liver crosstalk: mechanisms and therapeutic targets.Experimental & molecular medicine · 2026Review
- Cereblon enhances hepatic hepcidin production through estrogen-related receptor gamma activation.BMB reports · 2026Article
- Identification and Functional Characterization of an Ancestral Hepcidin-Like Antimicrobial Peptide in the Lamprey (Lethenteron camtschaticum).Probiotics and antimicrobial proteins · 2026Article
- The role of gut microbiota mediated ferroptosis in PCOS and the therapeutic potential of Chinese herbal medicine.Frontiers in medicine · 2026Review
- Targeting the gut microbiota: the application and prospects of probiotics, fecal microbiota transplantation, and natural products in MASLD.Frontiers in nutrition · 2026Review
- Article
- Hepatocyte Toll-like receptors contribute to the hepcidin inflammatory response to pathogens and pathogen-derived ligands.HemaSphere · 2025Article
- Molecular mechanisms and clinical applications of gut microbiota-derived bioactive compounds in metabolic dysfunction-associated fatty liver disease.Frontiers in immunology · 2025Review
- Review
- Hepatocyte activation and liver injury following cerebral ischemia promote HMGB1-mediated hepcidin upregulation in hepatocytes and regulation of systemic iron levels.Experimental & molecular medicine · 2024Article
- Direct and macrophage stimulation mediated effects of active, inactive, and cell-free supernatant forms of Akkermansia muciniphila and Faecalibacterium duncaniae on hepcidin gene expression in HepG2 cells.Archives of microbiology · 2024Article
- Interplay between gut microbiota and the master iron regulator, hepcidin, in the pathogenesis of liver fibrosis.Pathogens and disease · 2024Review
- HMGB1 induces hepcidin upregulation in astrocytes and causes an acute iron surge and subsequent ferroptosis in the postischemic brain.Experimental & molecular medicine · 2023Article
- Melatonin Regulates Iron Homeostasis by Inducing Hepcidin Expression in Hepatocytes.International journal of molecular sciences · 2022Article
- Links between Insulin Resistance and Periodontal Bacteria: Insights on Molecular Players and Therapeutic Potential of Polyphenols.Biomolecules · 2022Review
- Airway Epithelial Cells Differentially Adapt Their Iron Metabolism to Infection WithFrontiers in cellular and infection microbiology · 2022Article
- Brain-gut-liver axis: Chronic psychological stress promotes liver injury and fibrosisFrontiers in cellular and infection microbiology · 2022Article
- Molecular and Cellular Mechanisms Influenced by Postbiotics.International journal of molecular sciences · 2021Review
- Gut microbiota and immune system in liver cancer: Promising therapeutic implication from development to treatment.World journal of gastrointestinal oncology · 2021Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepcidin expression is induced by inflammatory molecules such as lipopolysaccharide (LPS) via a macrophage-mediated pathway. Although hepatocytes directly respond to LPS, the molecular mechanism underlying toll-like receptor (TLR)-dependent hepcidin expression by hepatocytes is mostly unknown. Here we show that LPS can directly induce the mRNA expression and secretion of hepcidin by hepatocytes via TLR4 activation. Using hepatocytes deficient in TLR4, myeloid differentiation factor 88 (MyD88) and TIR domain-containing adaptor inducing interferon-β (TRIF), we demonstrated that LPS-induced hepcidin expression by hepatocytes is regulated by its specific receptor, TLR4, via a MyD88-dependent signaling pathway. Hepcidin promoter activity was significantly increased by MyD88-dependent downstream signaling molecules (interleukin-1 receptor-associated kinase (IRAK) and tumor necrosis factor receptor-associated factor 6 (TRAF6), which activate c-Jun N-terminal kinase (JNK) and activator protein-1 (AP-1). We then confirmed that LPS stimulation induced the phosphorylation of JNK and c-Jun, and observed strong occupancy of the hepcidin promoter by c-Jun. Promoter mutation analysis also identified the AP-1-binding site on the hepcidin promoter. Finally, bone marrow transplantation between wild-type and TLR4 knockout mice revealed that hepatic TLR4-dependent hepcidin expression was comparable to macrophage TLR4-dependent hepcidin expression induced by LPS. Taken together, these results suggest that TLR4 expressed by hepatocytes regulates hepcidin expression via the IRAK-TRAF6-JNK-AP-1 axis.
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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.