title: Regulation of Hepcidin by Erythropoiesis: The Story So Far.
abstract: Hepcidin is the master regulator of systemic iron homeostasis, facilitating iron balance by controlling intestinal iron absorption and recycling. Hepcidin levels are suppressed when erythropoiesis is stimulated, for example following acute blood loss, appropriately enhancing cellular iron export to the plasma to support production of new red blood cells. However, persistent increased and ineffective erythropoiesis, for example in thalassemia, results in sustained elevations in iron absorption, which cause iron overload with associated organ toxicities. The ligands, receptors, and canonical pathways by which iron loading and inflammation upregulate hepcidin expression have been largely established. However, although several mechanisms have been proposed, the means by which erythropoiesis causes hepcidin suppression have been unclear. The erythroid-derived hormone erythroferrone appears to be a convincing candidate for the link between increased erythropoiesis and hepcidin suppression. If confirmed to be clinically and physiologically relevant in humans, potentiation or inhibition of erythroferrone activity could be a crucial pharmaceutical strategy.
authors.affiliation: Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute for Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom; email: sant-rayn.pasricha@ndm.ox.ac.uk.
authors.forename: Sant-Rayn
authors.initials: SR
authors.lastname: Pasricha
authors.affiliation: Jenner Institute, University of Oxford, Oxford OX3 7DQ, United Kingdom.
authors.forename: Kirsty
authors.initials: K
authors.lastname: McHugh
authors.affiliation: Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute for Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom; email: sant-rayn.pasricha@ndm.ox.ac.uk.
authors.forename: Hal
authors.initials: H
authors.lastname: Drakesmith
mesh_terms: D000818:Animals; D015536:Down-Regulation; D004920:Erythropoiesis; D019317:Evidence-Based Medicine; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D064451:Hepcidins / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism; D008024:Ligands; D008954:Models, Biological; D036361:Peptide Hormones / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C000600298:Erfe protein, human; C578702:HAMP protein, human; D064451:Hepcidins; D008024:Ligands; D036361:Peptide Hormones; D007501:Iron
keywords: erythroferrone; erythropoiesis; hepcidin; iron; thalassemia