ArticleWorld journal of hepatology2021
Direct modulation of hepatocyte hepcidin signaling by iron.
Article in World journal of hepatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 14 citations in OpenAlex.
- Ambrisentan Exhibits Hepatoprotective Effects Against NASH-Associated Hepatic Injury in Dexamethasone-Treated Rats Through Regulation of Inflammation, Ferroptosis and Autophagy.Pharmaceuticals (Basel, Switzerland) · 2026Article
- HFE-Related Hemochromatosis May Be a Primary Kupffer Cell Disease.Biomedicines · 2025Review
- Iron homeostasis and insulin sensitivity: unraveling the complex interactions.Reviews in endocrine & metabolic disorders · 2024Review
- Low intensity near-infrared light promotes bone regeneration via circadian clock protein cryptochrome 1.International journal of oral science · 2022Article
- Article
- Emerging Roles of the Iron Chelators in Inflammation.International journal of molecular sciences · 2022Review
- Novel Insights into Alcoholic Liver Disease: Iron Overload, Iron Sensing and Hemolysis.Journal of translational internal medicine · 2022Article
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Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLiver-secreted hepcidin is the systemic master switch of iron homeostasis and decreased levels of hepcidin are considered to cause iron overload not only in hereditary hemochromatosis but also in hemolytic anemia and chronic liver diseases. The regulation of hepcidin is complex and its response to iron is still not completely understood.
aimTo study the direct effect of iron on various established hepcidin signaling pathways in hepatoma cells or primary hepatocytes.
methodsHepcidin mRNA expression was studied by quantitative real-time (qRT)-PCR in the presence of various forms of iron including ferric ammonium citrate (FAC) in hepatoma cells (Huh7), murine primary hepatocytes and an established co-culture model of phorbol myristate acetate-differentiated THP-1 monocytes and Huh7 cells. To analyze hepcidin signaling, the response to bone morphogenetic protein 6 (BMP6), interleukin (IL)-6, IL-1β, hypoxia and lipopolysaccharide (LPS) were studied. Hepcidin and small mothers against decapentaplegic 6 (SMAD6) mRNA levels were assessed by qRT-PCR and the expression of phosphorylated signal transducer and activator of transcription 3 (phospho-STAT3), STAT3, phospho-SMAD1/5/8 and SMAD1 proteins were analyzed by western blot.
resultsAll iron III forms including FAC efficiently blocked hepcidin mRNA expression at non-toxic dosages in Huh7 cells or primary hepatocytes in a time and dose-dependent manner (
conclusionIron directly blocks hepatocellular hepcidin signaling through the BMP/SMAD pathway but independent of STAT3. This mechanism may contribute to continued iron overload in many pathophysiological conditions ultimately causing a vicious cycle of continued hepcidin suppression.
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