ArticleThe Journal of biological chemistry2010
Soluble repulsive guidance molecule c/hemojuvelin is a broad spectrum bone morphogenetic protein (BMP) antagonist and inhibits both BMP2- and BMP6-mediated signaling and gene expression.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Pooled it
- Hemojuvelin-mediated hepcidin induction requires both bone morphogenetic protein type I receptors ALK2 and ALK3.Blood advances · 2024Article
- Novel potential therapeutics to modify iron metabolism and red cell synthesis in diseases associated with defective erythropoiesis.Haematologica · 2023Review
- Activation of STAT and SMAD Signaling Induces Hepcidin Re-Expression as a Therapeutic Target for β-Thalassemia Patients.Biomedicines · 2022Review
- TGF-β superfamily co-receptors in cancer.Developmental dynamics : an official publication of the American Association of Anatomists · 2022Review
- Matriptase-2 and Hemojuvelin in Hepcidin Regulation: In Vivo Immunoblot Studies inInternational journal of molecular sciences · 2021Article
- Ineffective Erythropoiesis: Anemia and Iron Overload.Hematology/oncology clinics of North America · 2018Review
- Iron in the Tumor Microenvironment-Connecting the Dots.Frontiers in oncology · 2018Review
- Effect of erythropoietin administration on proteins participating in iron homeostasis in Tmprss6-mutated mask mice.PloS one · 2017Article
- Bone Morphogenetic Proteins.Cold Spring Harbor perspectives in biology · 2016Review
- Anti-hemojuvelin antibody corrects anemia caused by inappropriately high hepcidin levels.Haematologica · 2016Article
- Effect of Erythropoietin, Iron Deficiency and Iron Overload on Liver Matriptase-2 (TMPRSS6) Protein Content in Mice and Rats.PloS one · 2016Article
- HJV and HFE Play Distinct Roles in Regulating Hepcidin.Antioxidants & redox signaling · 2015Article
- Identification of TMPRSS6 cleavage sites of hemojuvelin.Journal of cellular and molecular medicine · 2015Article
- The pathophysiology and pharmacology of hepcidin.Trends in pharmacological sciences · 2014Review
- Bone morphogenetic proteins as regulators of iron metabolism.Annual review of nutrition · 2014Review
- Manipulation of the hepcidin pathway for therapeutic purposes.Haematologica · 2013Review
- Repulsive guidance molecules (RGMs) and neogenin in bone morphogenetic protein (BMP) signaling.Molecular reproduction and development · 2013Review
- Iron regulation by hepcidin.The Journal of clinical investigation · 2013Article
- Proteomic analysis and molecular modelling characterize the iron-regulatory protein haemojuvelin/repulsive guidance molecule c.The Biochemical journal · 2013Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Inactivating mutations in hemojuvelin/repulsive guidance molecule c (HJV/RGMc) cause juvenile hemochromatosis (JH), a rapidly progressive iron overload disorder in which expression of hepcidin, a key liver-derived iron-regulatory hormone, is severely diminished. Several growth factors in the bone morphogenetic protein (BMP) family, including BMP2 and BMP6, can stimulate production of hepcidin, a biological effect that may be modified by RGMc. Here we demonstrate that soluble RGMc proteins are potent BMP inhibitors. We find that 50- and 40-kDa RGMc isoforms, when added to cells as highly purified IgG Fc fusion proteins, are able to block the acute effects of both BMP2 and BMP6 at the levels of Smad induction and gene activation, and thus represent a potentially unique class of broad-spectrum BMP antagonists. Whole transcript microarray analysis revealed that BMP2 and BMP6 each stimulated expression of a nearly identical cohort of approximately 40 mRNAs in Hep3B cells and demonstrated that 40-kDa RGMc was an effective inhibitor of both growth factors, although its potency was less than that of the known BMP2-selective antagonist, Noggin. We additionally show that JH-linked RGMc mutant proteins that retain the ability to bind BMPs are also able to function as BMP inhibitors, and like the wild type soluble RGMc species, can block BMP-activated hepcidin gene expression. The latter results raise the question of whether disease severity in JH will vary depending on the ability of a given mutant RGMc protein to interact with BMPs.
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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.