ArticleBlood2014
HFE interacts with the BMP type I receptor ALK3 to regulate hepcidin expression.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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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.
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Who cites it
55 citing papers in PubMed, 125 citations in OpenAlex.
- The neogenin-hemojuvelin axis in murine liver is crucial for hepcidin expression.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Control of Systemic Iron Homeostasis: Insights Gained from Studying Mouse Models.Advances in experimental medicine and biology · 2025Review
- Serum Iron Overload Activates the SMAD Pathway and Hepcidin Expression of Hepatocytes via SMURF1.Journal of clinical and translational hepatology · 2024Article
- Article
- Interpreting Iron Homeostasis in Congenital and Acquired Disorders.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Transferrin receptor 1: keeper of HFE.Blood · 2023Article
- Article
- Engineering Peptide Inhibitors of the HFE-Transferrin Receptor 1 Complex.Molecules (Basel, Switzerland) · 2022Article
- Novel Insights into Alcoholic Liver Disease: Iron Overload, Iron Sensing and Hemolysis.Journal of translational internal medicine · 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
- Physiology and Inflammation Driven Pathophysiology of Iron Homeostasis-Mechanistic Insights into Anemia of Inflammation and Its Treatment.Nutrients · 2021Review
- Epigallocatechin-3-Gallate Suppresses BMP-6-Mediated SMAD1/5/8 Transactivation of Hepcidin Gene by Inducing SMILE in Hepatocytes.Antioxidants (Basel, Switzerland) · 2021Article
- Ethnic Differences in Iron Status.Advances in nutrition (Bethesda, Md.) · 2021Review
- HFE inhibits type I IFNs signaling by targeting the SQSTM1-mediated MAVS autophagic degradation.Autophagy · 2021Article
- Hepcidin Signaling in Health and Disease: Ironing Out the Details.Hepatology communications · 2021Review
- Hereditary hemochromatosis promotes colitis and colon cancer and causes bacterial dysbiosis in mice.The Biochemical journal · 2020Article
- General Aspects of Metal Ions as Signaling Agents in Health and Disease.Biomolecules · 2020Review
- 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
- Hereditary hemochromatosis disrupts uric acid homeostasis and causes hyperuricemia via altered expression/activity of xanthine oxidase and ABCG2.The Biochemical journal · 2020Article
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
Mutations in HFE are the most common cause of hereditary hemochromatosis (HH). HFE mutations result in reduced expression of hepcidin, a hepatic hormone, which negatively regulates iron absorption from the duodenum and iron release from macrophages. However, the mechanism by which HFE regulates hepcidin expression in hepatocytes is not well understood. It is known that the bone morphogenetic protein (BMP) pathway plays a central role in controlling hepcidin expression in the liver. Here we show that HFE overexpression increased Smad1/5/8 phosphorylation and hepcidin expression, whereas inhibition of BMP signaling abolished HFE-induced hepcidin expression in Hep3B cells. HFE was found to associate with ALK3, inhibiting ALK3 ubiquitination and proteasomal degradation and increasing ALK3 protein expression and accumulation on the cell surface. The 2 HFE mutants associated with HH, HFE C282Y and HFE H63D, regulated ALK3 protein ubiquitination and trafficking differently, but both failed to increase ALK3 cell-surface expression. Deletion of Hfe in mice resulted in a decrease in hepatic ALK3 protein expression. Our results provide evidence that HFE induces hepcidin expression via the BMP pathway: HFE interacts with ALK3 to stabilize ALK3 protein and increase ALK3 expression at the cell surface.
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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.