ArticleGastroenterology2011
Iron regulation of hepcidin despite attenuated Smad1,5,8 signaling in mice without transferrin receptor 2 or Hfe.
Article in Gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 96 citations in OpenAlex.
- Inactivation of major hepcidin pathways leads to systemic and hepatic iron overload during development of chemically-induced liver cirrhosis in rats.Journal of toxicologic pathology · 2025Article
- Iron and Liver Disease.Advances in experimental medicine and biology · 2025Review
- Control of Systemic Iron Homeostasis: Insights Gained from Studying Mouse Models.Advances in experimental medicine and biology · 2025Review
- Effects of iron overload in human joint tissue explant cultures and animal models.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Review
- Article
- DENND3 p.L708V activating variant is involved in the pathogenesis of hereditary hemochromatosis via the RAB12/TFR2 signaling pathway.Hepatology international · 2023Article
- Interpreting Iron Homeostasis in Congenital and Acquired Disorders.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Article
- Haemochromatosis revisited.World journal of hepatology · 2022Review
- Transferrin receptor 2 (Tfr2) genetic deletion makes transfusion-independent a murine model of transfusion-dependent β-thalassemia.American journal of hematology · 2022Article
- 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
- General Aspects of Metal Ions as Signaling Agents in Health and Disease.Biomolecules · 2020Review
- Review
- Ablation of Hepatocyte Smad1, Smad5, and Smad8 Causes Severe Tissue Iron Loading and Liver Fibrosis in Mice.Hepatology (Baltimore, Md.) · 2019Article
- Lobe specificity of iron binding to transferrin modulates murine erythropoiesis and iron homeostasis.Blood · 2019Article
- Despite Genetic Iron Overload,JBMR plus · 2019Article
- Phospholipase C (PLC)ε Promotes Androgen Receptor Antagonist Resistance via the Bone Morphogenetic Protein (BMP)-6/SMAD Axis in a Castration-Resistant Prostate Cancer Cell Line.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- Deregulation of Hepatic Mek1/2⁻Erk1/2 Signaling Module in Iron Overload Conditions.Pharmaceuticals (Basel, Switzerland) · 2019Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsHFE and transferrin receptor 2 (TFR2) are each necessary for the normal relationship between body iron status and liver hepcidin expression. In murine Hfe and Tfr2 knockout models of hereditary hemochromatosis (HH), signal transduction to hepcidin via the bone morphogenetic protein 6 (Bmp6)/Smad1,5,8 pathway is attenuated. We examined the effect of dietary iron on regulation of hepcidin expression via the Bmp6/Smad1,5,8 pathway using mice with targeted disruption of Tfr2, Hfe, or both genes.
methodsHepatic iron concentrations and messenger RNA expression of Bmp6 and hepcidin were compared with wild-type mice in each of the HH models on standard or iron-loading diets. Liver phospho-Smad (P-Smad)1,5,8 and Id1 messenger RNA levels were measured as markers of Bmp/Smad signaling.
resultsWhereas Bmp6 expression was increased, liver hepcidin and Id1 expression were decreased in each of the HH models compared with wild-type mice. Each of the HH models also showed attenuated P-Smad1,5,8 levels relative to liver iron status. Mice with combined Hfe/Tfr2 disruption were most affected. Dietary iron loading increased hepcidin and Id1 expression in each of the HH models. Compared with wild-type mice, HH mice demonstrated attenuated (Hfe knockout) or no increases in P-Smad1,5,8 levels in response to dietary iron loading.
conclusionsThese observations show that Tfr2 and Hfe are each required for normal signaling of iron status to hepcidin via the Bmp6/Smad1,5,8 pathway. Mice with combined loss of Hfe and Tfr2 up-regulate hepcidin in response to dietary iron loading without increases in liver Bmp6 messenger RNA or steady-state P-Smad1,5,8 levels.
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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.