ArticleHepatology (Baltimore, Md.)2012
Inhibition of hepcidin transcription by growth factors.
Article in Hepatology (Baltimore, Md.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 104 citations in OpenAlex.
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- Iron, the Essential Micronutrient: A Comprehensive Review of Regulatory Pathways of Iron Metabolism.Nutrients · 2025Review
- Hepatocyte growth factor alleviates alcoholic cardiomyopathy through the Nrf2 pathway-a focus on iron metabolism.Journal of thoracic disease · 2025Article
- Ablation of Hepatocyte Derived-FGL1 Does Not Aggravate Metabolic Dysfunction-Associated Steatotic Liver Disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Molecular Mechanisms of Iron Metabolism and Overload.Biomedicines · 2025Review
- Iron Status in Sport Horses: Is It Important for Equine Athletes?International journal of molecular sciences · 2025Review
- The effect of iron supplementation in preterm infants at different gestational ages.BMC pediatrics · 2024Article
- Human umbilical cord mesenchymal stem cells protect against ferroptosis in acute liver failure through the IGF1-hepcidin-FPN1 axis and inhibiting iron loading.Acta biochimica et biophysica Sinica · 2024Article
- Protective Effects and Mechanism of Polysaccharides from Edible Medicinal Plants in Alcoholic Liver Injury: A Review.International journal of molecular sciences · 2023Review
- Iron homeostasis in full-term, normal birthweight Gambian neonates over the first week of life.Scientific reports · 2023Article
- Distinctive modulation of hepcidin in cancer and its therapeutic relevance.Frontiers in oncology · 2023Review
- Iron overload in alcoholic liver disease: underlying mechanisms, detrimental effects, and potential therapeutic targets.Cellular and molecular life sciences : CMLS · 2022Review
- A contemporary understanding of iron metabolism in active premenopausal females.Frontiers in sports and active living · 2022Review
- Coordination of iron homeostasis by bone morphogenetic proteins: Current understanding and unanswered questions.Developmental dynamics : an official publication of the American Association of Anatomists · 2022Article
- Physiological and pathophysiological mechanisms of hepcidin regulation: clinical implications for iron disorders.British journal of haematology · 2021Review
- Hepcidin Signaling in Health and Disease: Ironing Out the Details.Hepatology communications · 2021Review
- Iron Homeostasis and Hepcidin Concentration in Patients With Acromegaly.Frontiers in endocrinology · 2021Article
- Expression of Iron-Regulatory Hormone Hepcidin and Iron Transporters Ferroportin and ZIP8 in Patients With and Without Chronic Rhinosinusitis.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2020Article
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Authors and funding
4 authors at 1 institution in 1 country.
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Abstract
unlabelledThe hepatic peptide hormone hepcidin controls the duodenal absorption of iron, its storage, and its systemic distribution. Hepcidin production is often insufficient in chronic hepatitis C and alcoholic liver disease, leading to hyperabsorption of iron and its accumulation in the liver. Hepatocyte growth factor (HGF) and epidermal growth factor (EGF) mediate hepatic regeneration after liver injury. We examined the effect of these growth factors on hepcidin synthesis by hepatocytes. HGF and EGF treatment of primary mouse hepatocytes, as well as EGF administration in mice, suppressed hepcidin messenger RNA (mRNA) synthesis. The suppression of hepcidin by these growth factors was transcriptional, and was mediated by a direct effect of HGF and EGF on the bone morphogenetic protein (BMP) pathway regulating hepcidin synthesis. We further show that growth factors interfered with nuclear localization of activated sons of mothers against decapentaplegic (Smad) and increased the nuclear pool of the BMP transcriptional corepressor TG-interacting factor (TGIF). In a kinase screen with small-molecule kinase inhibitors, inhibitors in the PI3 kinase pathway and in the mitogen-activated ERK kinase/extracellular signal-regulated kinase (MEK/ERK) pathway prevented HGF suppression of hepcidin in primary mouse hepatocytes.
conclusionHGF and EGF suppress hepatic hepcidin synthesis, in part through PI3 kinase MEK/ERK kinase pathways which may be modulating the nuclear localization of BMP pathway transcriptional regulators including activated Smads1/5/8 and the corepressor TGIF. EGF, HGF, and possibly other growth factors that activate similar pathways may contribute to hepcidin suppression in chronic liver diseases, promote iron accumulation in the liver, and exacerbate the destructive disease processes.
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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.