ArticleJournal of molecular medicine (Berlin, Germany)2015
Hfe and Hjv exhibit overlapping functions for iron signaling to hepcidin.
Article in Journal of molecular medicine (Berlin, Germany), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Pooled it
- The neogenin-hemojuvelin axis in murine liver is crucial for hepcidin expression.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Bone phenotyping of murine hemochromatosis models with deficiencies of Hjv, Alk2, or Alk3: The influence of sex and the bone compartment.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Article
- Evidence That HFE H63D Variant Is a Potential Disease Modifier in Cluster Headache.Journal of molecular neuroscience : MN · 2022Article
- Tissue-Specific Regulation of Ferroportin in Wild-Type and Hjv-/- Mice Following Dietary Iron Manipulations.Hepatology communications · 2021Article
- Hepcidin Signaling in Health and Disease: Ironing Out the Details.Hepatology communications · 2021Review
- Interplay Between Iron Overload and Osteoarthritis: Clinical Significance and Cellular Mechanisms.Frontiers in cell and developmental biology · 2021Review
- Regulation of Iron Homeostasis and Related Diseases.Mediators of inflammation · 2020Review
- New thiazolidinones reduce iron overload in mouse models of hereditary hemochromatosis and β-thalassemia.Haematologica · 2019Article
- Iron induces insulin resistance in cardiomyocytes via regulation of oxidative stress.Scientific reports · 2019Article
- Mouse models of hereditary hemochromatosis do not develop early liver fibrosis in response to a high fat diet.PloS one · 2019Article
- ALK3 undergoes ligand-independent homodimerization and BMP-induced heterodimerization with ALK2.Free radical biology & medicine · 2018Article
- MyD88 Adaptor Protein Is Required for Appropriate Hepcidin Induction in Response to Dietary Iron Overload in Mice.Frontiers in physiology · 2018Article
- Inherited Disorders of Iron Overload.Frontiers in nutrition · 2018Review
- Matriptase-2 suppresses hepcidin expression by cleaving multiple components of the hepcidin induction pathway.The Journal of biological chemistry · 2017Article
- Minor variant of rs 16827043 in the iron regulator hemojuvelin gene (HJV) contributes to hypertension: The TAMRISK study.Medicine · 2017Article
- Deficits of learning and memory in Hemojuvelin knockout mice.The Journal of veterinary medical science · 2015Article
- Blood and iron.Journal of molecular medicine (Berlin, Germany) · 2015Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
unlabelledFunctional inactivation of HFE or hemojuvelin (HJV) is causatively linked to adult or juvenile hereditary hemochromatosis, respectively. Systemic iron overload results from inadequate expression of hepcidin, the iron regulatory hormone. While HJV regulates hepcidin by amplifying bone morphogenetic protein (BMP) signaling, the role of HFE in the hepcidin pathway remains incompletely understood. We investigated the pathophysiological implications of combined Hfe and Hjv ablation in mice. Isogenic Hfe (-)/(-) and Hjv (-)/(-) mice were crossed to generate double Hfe (-)/(-) Hjv (-)/(-) progeny. Wild-type control and mutant mice of all genotypes were analyzed for serum, hepatic, and splenic iron content, expression of iron metabolism proteins, and expression of hepcidin and Smad signaling in the liver, in response to a standard or an iron-enriched diet. As expected, Hfe (-)/(-) and Hjv (-)/(-) mice developed relatively mild or severe iron overload, respectively, which corresponded to the degree of hepcidin inhibition. The double Hfe (-)/(-) Hjv (-)/(-) mice exhibited an indistinguishable phenotype to single Hjv (-)/(-) counterparts with regard to suppression of hepcidin, serum and hepatic iron overload, splenic iron deficiency, tissue iron metabolism, and Smad signaling, under both dietary regimens. We conclude that the hemochromatotic phenotype caused by disruption of Hjv is not further aggravated by combined Hfe/Hjv deficiency. Our results provide genetic evidence that Hfe and Hjv operate in the same pathway for the regulation of hepcidin expression and iron metabolism. KEY MESSAGES: Combined disruption of Hfe and Hjv phenocopies single Hjv deficiency. Single Hjv(-)/(-) and double Hfe(-)/(-)Hjv(-)/(-) mice exhibit comparable iron overload. Hfe and Hjv regulate hepcidin via the same pathway.
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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.