ArticleGastroenterology2009
Bone morphogenetic protein signaling is impaired in an HFE knockout mouse model of hemochromatosis.
Article in Gastroenterology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 140 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
- HFE-Related Hemochromatosis May Be a Primary Kupffer Cell Disease.Biomedicines · 2025Review
- 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
- Hereditary hemochromatosis with homozygous C282Y HFE mutation: possible clinical model to assess effects of elevated reactive oxygen species on the development of cardiovascular disease.Molecular and cellular biochemistry · 2024Review
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- Functional role of endothelial transferrin receptor 1 in iron sensing and homeostasis.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
- Iron Accumulation and Lipid Peroxidation in the Aging Retina: Implication of Ferroptosis in Age-Related Macular Degeneration.Aging and disease · 2021Review
- Review
- Review
- Endothelial Bone Morphogenetic Protein 2 (Bmp2) Knockout Exacerbates Hemochromatosis in Homeostatic Iron Regulator (Hfe) Knockout Mice but not Bmp6 Knockout Mice.Hepatology (Baltimore, Md.) · 2020Article
- Porphyria cutanea tarda associated with elevated serum ferritin, iron overload, and a bone morphogenetic protein 6 genetic variant.Canadian liver journal · 2020Article
- Ablation of Hepatocyte Smad1, Smad5, and Smad8 Causes Severe Tissue Iron Loading and Liver Fibrosis in Mice.Hepatology (Baltimore, Md.) · 2019Article
- Despite Genetic Iron Overload,JBMR plus · 2019Article
- Erythropoietic regulators of iron metabolism.Free radical biology & medicine · 2019Review
- Iron, erythropoietin, and inflammation regulate hepcidin in Bmp2-deficient mice, but serum iron fails to induce hepcidin in Bmp6-deficient mice.American journal of hematology · 2019Article
- Liver iron sensing and body iron homeostasis.Blood · 2019Review
- The hemochromatosis protein HFE signals predominantly via the BMP type I receptor ALK3 in vivo.Communications biology · 2018Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
aimsMutations in HFE are the most common cause of the iron-overload disorder hereditary hemochromatosis. Levels of the main iron regulatory hormone, hepcidin, are inappropriately low in hereditary hemochromatosis mouse models and patients with HFE mutations, indicating that HFE regulates hepcidin. The bone morphogenetic protein 6 (BMP6)-SMAD signaling pathway is an important endogenous regulator of hepcidin expression. We investigated whether HFE is involved in BMP6-SMAD regulation of hepcidin expression.
methodsThe BMP6-SMAD pathway was examined in Hfe knockout (KO) mice and in wild-type (WT) mice as controls. Mice were placed on diets of varying iron content. Hepcidin induction by BMP6 was examined in primary hepatocytes from Hfe KO mice; data were compared with those of WT mice.
resultsLiver levels of Bmp6 messenger RNA (mRNA) were higher in Hfe KO mice; these were appropriate for the increased hepatic levels of iron in these mice, compared with WT mice. However, levels of hepatic phosphorylated Smad 1/5/8 protein (an intracellular mediator of Bmp6 signaling) and Id1 mRNA (a target gene of Bmp6) were inappropriately low for the body iron burden and Bmp6 mRNA levels in Hfe KO, compared with WT mice. BMP6 induction of hepcidin expression was reduced in Hfe KO hepatocytes compared with WT hepatocytes.
conclusionsHFE is not involved in regulation of BMP6 by iron, but does regulate the downstream signals of BMP6 that are triggered by iron.
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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.