title: Targeting the hepcidin-ferroportin axis to develop new treatment strategies for anemia of chronic disease and anemia of inflammation.
abstract: Anemia of chronic disease (ACD) or anemia of inflammation is prevalent in patients with chronic infection, autoimmune disease, cancer, and chronic kidney disease. ACD is associated with poor prognosis and lower quality of life. Management of ACD using intravenous iron and erythropoiesis stimulating agents are ineffective for some patients and are not without adverse effects, driving the need for new alternative therapies. Recent advances in our understanding of the molecular mechanisms of iron regulation reveal that increased hepcidin, the iron regulatory hormone, is a key factor in the development of ACD. In this review, we will summarize the role of hepcidin in iron homeostasis, its contribution to the pathophysiology of ACD, and novel strategies that modulate hepcidin and its target ferroportin for the treatment of ACD.
authors.affiliation: Program in Membrane Biology, Division of Nephrology, Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Chia Chi
authors.initials: CC
authors.lastname: Sun
authors.forename: Valentina
authors.initials: V
authors.lastname: Vaja
authors.forename: Jodie L
authors.initials: JL
authors.lastname: Babitt
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Lin
mesh_terms: D000740:Anemia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology / Q000502:physiology / Q000633:toxicity; D055418:Bone Morphogenetic Protein 6 / Q000037:antagonists & inhibitors / Q000502:physiology; D027682:Cation Transport Proteins / Q000819:agonists* / Q000502:physiology; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000503:physiopathology; D007501:Iron / Q000378:metabolism*; D051379:Mice; D058990:Molecular Targeted Therapy; D011720:Pyrazoles / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D034741:RNA, Small Interfering / Q000627:therapeutic use; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D051785:Smad Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D035703:Therapies, Investigational; D014807:Vitamin D / Q000627:therapeutic use; D000098742:Ferroportin; D000093242:Interleukin-6 Inhibitors; D015850:Interleukin-6
chemical_list: D000911:Antibodies, Monoclonal; D023181:Antimicrobial Cationic Peptides; D055418:Bone Morphogenetic Protein 6; D027682:Cation Transport Proteins; D058851:GPI-Linked Proteins; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D007501:Iron; D011720:Pyrazoles; D011743:Pyrimidines; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D051785:Smad Proteins; D014807:Vitamin D; D000098742:Ferroportin; D000093242:Interleukin-6 Inhibitors; C525816:BMP6 protein, human; C578702:HAMP protein, human; C481006:HJV protein, human; C579599:Hamp protein, mouse; C508600:IL6 protein, human; D015850:Interleukin-6; C554430:LDN 193189; C494086:STAT3 protein, human