ArticleBlood2017
Endothelial cells produce bone morphogenetic protein 6 required for iron homeostasis in mice.
Article in Blood, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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Who cites it
117 citing papers in PubMed, 207 citations in OpenAlex.
- The neogenin-hemojuvelin axis in murine liver is crucial for hepcidin expression.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Ferroptosis in liver biology and diseases.Hepatology communications · 2026Review
- Identification of Peroxisome Proliferator-Activated Receptors as Novel Regulators of Bovine Hepcidin Expression.Biochemical genetics · 2026Article
- A lactylation- and autophagy-associated prognostic signature reveals LSEC-derived CLEC3B as a novel mediator of hepatocellular carcinoma suppression.PLoS computational biology · 2026Article
- Halofuginone suppresses hepcidin by a heparan sulfate-dependent mechanism to treat iron disorders in mice.Blood advances · 2026Article
- Liver sinusoidal endothelial cells constitute a major route for hemoglobin clearance.EMBO reports · 2026Article
- Serum Hepcidin Levels are Associated with Poor Outcomes of Patients with Severe Traumatic Brain Injury: A Two-Center Observational Analytical Study.International journal of general medicine · 2026Article
- Zonation, Zonation, Zonation: The Real Estate of the Liver.Annual review of pathology · 2026Review
- Endothelial BMP6 Drives Hemodynamic-Dependent VSMCs Calcification in Carotid Atherosclerosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Ferroptosis in liver fibrosis and its potential intervention strategy.Cell biology and toxicology · 2025Review
- A Recombinant Antibody Against ALK2 Promotes Tissue Iron Redistribution and Contributes to Anemia Resolution in a Mouse Model of Anemia of Inflammation.American journal of hematology · 2025Article
- Article
- Systemic Iron Metabolism.Advances in experimental medicine and biology · 2025Review
- 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
- Sevuparin strongly reduces hepcidin expression in cells, mice, and healthy human volunteers.HemaSphere · 2024Article
- Article
- The prodomain of bone morphogenetic protein 2 promotes dimerization and cleavage of BMP6 homodimers and BMP2/6 heterodimers.The Journal of biological chemistry · 2024Article
- Hemojuvelin-mediated hepcidin induction requires both bone morphogenetic protein type I receptors ALK2 and ALK3.Blood advances · 2024Article
- Article
57 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Bone morphogenetic protein 6 (BMP6) signaling in hepatocytes is a central transcriptional regulator of the iron hormone hepcidin that controls systemic iron balance. How iron levels are sensed to regulate hepcidin production is not known, but local induction of liver BMP6 expression by iron is proposed to have a critical role. To identify the cellular source of BMP6 responsible for hepcidin and iron homeostasis regulation, we generated mice with tissue-specific ablation of Bmp6 in different liver cell populations and evaluated their iron phenotype. Efficiency and specificity of Cre-mediated recombination was assessed by using Cre-reporter mice, polymerase chain reaction of genomic DNA, and quantitation of Bmp6 messenger RNA expression from isolated liver cell populations. Localization of the BMP co-receptor hemojuvelin was visualized by immunofluorescence microscopy. Analysis of the Bmp6 conditional knockout mice revealed that liver endothelial cells (ECs) expressed Bmp6, whereas resident liver macrophages (Kupffer cells) and hepatocytes did not. Loss of Bmp6 in ECs recapitulated the hemochromatosis phenotype of global Bmp6 knockout mice, whereas hepatocyte and macrophage Bmp6 conditional knockout mice exhibited no iron phenotype. Hemojuvelin was localized on the hepatocyte sinusoidal membrane immediately adjacent to Bmp6-producing sinusoidal ECs. Together, these data demonstrate that ECs are the predominant source of BMP6 in the liver and support a model in which EC BMP6 has paracrine actions on hepatocyte hemojuvelin to regulate hepcidin transcription and maintain systemic iron homeostasis.
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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.