ArticleBlood2017
The immunophilin FKBP12 inhibits hepcidin expression by binding the BMP type I receptor ALK2 in hepatocytes.
Article in Blood, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 56 citations in OpenAlex.
- Increased levels of systemic iron content in adult-onset interleukin-6 knockout mice.Redox report : communications in free radical research · 2026Article
- Hepcidin as a Molecular Hub of Iron Homeostasis: From BMP-SMAD Signaling to Therapeutic Modulation.Biomolecules · 2026Review
- Targeting the Liver Serine Protease TMPRSS6 Ameliorates Steatosis and Attenuates Fibrosis in Experimental MASLD.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- 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
- HFE-Related Hemochromatosis May Be a Primary Kupffer Cell Disease.Biomedicines · 2025Review
- Systemic Iron Metabolism.Advances in experimental medicine and biology · 2025Review
- Current Landscape of Hepcidin Therapeutics.Advances in experimental medicine and biology · 2025Review
- BMP-ACVR1 Axis is Critical for Efficacy of PRC2 Inhibitors in B-Cell Lymphoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Mechanisms controlling cellular and systemic iron homeostasis.Nature reviews. Molecular cell biology · 2024Review
- FK506 bypasses the effect of erythroferrone in cancer cachexia skeletal muscle atrophy.Cell reports. Medicine · 2023Article
- Flavor of Iron at EHA2023: Novel Regulatory Mechanisms and Therapeutic Options for the Correction of Anemia.HemaSphere · 2023Article
- Novel potential therapeutics to modify iron metabolism and red cell synthesis in diseases associated with defective erythropoiesis.Haematologica · 2023Review
- Recent developments on BMPs and their antagonists in inflammatory bowel diseases.Cell death discovery · 2023Review
- Duodenal macrophages control dietary iron absorption via local degradation of transferrin.Blood · 2023Article
- 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
- Review
- The mutual crosstalk between iron and erythropoiesis.International journal of hematology · 2022Review
- PROTAC mediated FKBP12 degradation enhances Hepcidin expression via BMP signaling without immunosuppression activity.Signal transduction and targeted therapy · 2022Article
- Novel Insights and Future Perspective in Iron Metabolism and Anemia.Metabolites · 2022Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The expression of the key regulator of iron homeostasis hepcidin is activated by the BMP-SMAD pathway in response to iron and inflammation and among drugs, by rapamycin, which inhibits mTOR in complex with the immunophilin FKBP12. FKBP12 interacts with BMP type I receptors to avoid uncontrolled signaling. By pharmacologic and genetic studies, we identify FKBP12 as a novel hepcidin regulator. Sequestration of FKBP12 by rapamycin or tacrolimus activates hepcidin both in vitro and in murine hepatocytes. Acute tacrolimus treatment transiently increases hepcidin in wild-type mice. FKBP12 preferentially targets the BMP receptor ALK2. ALK2 mutants defective in binding FKBP12 increase hepcidin expression in a ligand-independent manner, through BMP-SMAD signaling. ALK2 free of FKBP12 becomes responsive to the noncanonical inflammatory ligand Activin A. Our results identify a novel hepcidin regulator and a potential therapeutic target to increase defective BMP signaling in disorders of low hepcidin.
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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.