ArticlePloS one2015
Bmp6 expression in murine liver non parenchymal cells: a mechanism to control their high iron exporter activity and protect hepatocytes from iron overload?
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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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
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Methods for Isolation and Purification of Murine Liver Sinusoidal Endothelial Cells: A Systematic Review.PloS one · 2016Pooled it
- Iron Overload: Pathophysiology, Diagnosis and Monitoring.International journal of laboratory hematology · 2026Review
- BMP6 participates in the molecular mechanisms involved in APAP hepatotoxicity.Archives of toxicology · 2025Article
- 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
- Mechanisms controlling cellular and systemic iron homeostasis.Nature reviews. Molecular cell biology · 2024Review
- FLVCR1a Controls Cellular Cholesterol Levels through the Regulation of Heme Biosynthesis and Tricarboxylic Acid Cycle Flux in Endothelial Cells.Biomolecules · 2024Article
- Effects of a second iron-dextran injection administered to piglets during lactation on differential gene expression in liver and duodenum at weaning.Journal of animal science · 2024Article
- Oral Iron Absorption of Ferric Citrate Hydrate and Hepcidin-25 in Hemodialysis Patients: A Prospective, Multicenter, Observational Riona-Oral Iron Absorption Trial.International journal of molecular sciences · 2023Observational
- Intracellular labile iron is a key regulator of hepcidin expression and iron metabolism.Hepatology international · 2023Article
- Inaugurating a novel adjuvant therapy in urological cancers: Ferroptosis.Cancer pathogenesis and therapy · 2023Review
- Managing the Dual Nature of Iron to Preserve Health.International journal of molecular sciences · 2023Review
- Iron as a therapeutic target in chronic liver disease.World journal of gastroenterology · 2023Review
- Iron-dependent BMP6 Regulation in Liver Sinusoidal Endothelial Cells Is Instructed by Hepatocyte-derived Secretory Signals.HemaSphere · 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
- Runx3 regulates iron metabolism via modulation of BMP signalling.Cell proliferation · 2021Article
- Iron distribution in different tissues of homozygous Mask (msk/msk) mice and the effects of oral iron treatments.American journal of hematology · 2021Article
- Comparative Evaluation of Sucrosomial Iron and Iron Oxide Nanoparticles as Oral Supplements in Iron Deficiency Anemia in Piglets.International journal of molecular sciences · 2021Article
- Marginally reduced maternal hepatic and splenic ferroportin under severe nutritional iron deficiency in pregnancy maintains systemic iron supply.American journal of hematology · 2021Article
- Relationship between Down-Regulation of Copper-Related Genes and Decreased Ferroportin Protein Level in the Duodenum of Iron-Deficient Piglets.Nutrients · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Bmp6 is the main activator of hepcidin, the liver hormone that negatively regulates plasma iron influx by degrading the sole iron exporter ferroportin in enterocytes and macrophages. Bmp6 expression is modulated by iron but the molecular mechanisms are unknown. Although hepcidin is expressed almost exclusively by hepatocytes (HCs), Bmp6 is produced also by non-parenchymal cells (NPCs), mainly sinusoidal endothelial cells (LSECs). To investigate the regulation of Bmp6 in HCs and NPCs, liver cells were isolated from adult wild type mice whose diet was modified in iron content in acute or chronic manner and in disease models of iron deficiency (Tmprss6 KO mouse) and overload (Hjv KO mouse). With manipulation of dietary iron in wild-type mice, Bmp6 and Tfr1 expression in both HCs and NPCs was inversely related, as expected. When hepcidin expression is abnormal in murine models of iron overload (Hjv KO mice) and deficiency (Tmprss6 KO mice), Bmp6 expression in NPCs was not related to Tfr1. Despite the low Bmp6 in NPCs from Tmprss6 KO mice, Tfr1 mRNA was also low. Conversely, despite body iron overload and high expression of Bmp6 in NPCs from Hjv KO mice, Tfr1 mRNA and protein were increased. However, in the same cells ferritin L was only slightly increased, but the iron content was not, suggesting that Bmp6 in these cells reflects the high intracellular iron import and export. We propose that NPCs, sensing the iron flux, not only increase hepcidin through Bmp6 with a paracrine mechanism to control systemic iron homeostasis but, controlling hepcidin, they regulate their own ferroportin, inducing iron retention or release and further modulating Bmp6 production in an autocrine manner. This mechanism, that contributes to protect HC from iron loading or deficiency, is lost in disease models of hepcidin production.
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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.