Evidence for a Lack of a Direct Transcriptional Suppression of the Iron Regulatory Peptide Hepcidin by Hypoxia-Inducible Factors

A Krause, 2000, LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity., FEBS Lett, 480, 147, 10.1016/S0014-5793(00)01920-7

CH Park, 2001, Hepcidin, a urinary antimicrobial peptide synthesized in the liver., J Biol Chem, 276, 7806, 10.1074/jbc.M008922200

C Pigeon, 2001, A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload., J Biol Chem, 276, 7811, 10.1074/jbc.M008923200

G Nicolas, 2001, Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice., Proc Natl Acad Sci U S A, 98, 8780, 10.1073/pnas.151179498

E Nemeth, 2008, Iron regulation and erythropoiesis., Curr Opin Hematol, 15, 169, 10.1097/MOH.0b013e3282f73335

T Ganz, 2006, Iron imports. IV. Hepcidin and regulation of body iron metabolism., Am J Physiol Gastrointest Liver Physiol, 290, G199, 10.1152/ajpgi.00412.2005

SG Gehrke, 2003, Expression of hepcidin in hereditary hemochromatosis: evidence for a regulation in response to the serum transferrin saturation and to non-transferrin-bound iron., Blood, 102, 371, 10.1182/blood-2002-11-3610

E Nemeth, 2004, IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin., J Clin Invest, 113, 1271, 10.1172/JCI200420945

DM Wrighting, 2006, Interleukin-6 induces hepcidin expression through STAT3., Blood, 108, 3204, 10.1182/blood-2006-06-027631

MV Verga Falzacappa, 2007, STAT3 mediates hepatic hepcidin expression and its inflammatory stimulation., Blood, 109, 353, 10.1182/blood-2006-07-033969

P Lee, 2005, Regulation of hepcidin transcription by interleukin-1 and interleukin-6., Proc Natl Acad Sci U S A, 102, 1906, 10.1073/pnas.0409808102

E Beutler, 2006, Hemochromatosis: genetics and pathophysiology., Annu Rev Med, 57, 331, 10.1146/annurev.med.57.121304.131310

JL Babitt, 2006, Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression., Nat Genet, 38, 531, 10.1038/ng1777

T Tanno, 2007, High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin., Nat Med, 13, 1096, 10.1038/nm1629

B Courselaud, 2002, C/EBPα regulates hepatic transcription of hepcidin, an antimicrobial peptide and regulator of iron metabolism. Cross-talk between C/EBP pathway and iron metabolism., J Biol Chem, 277, 41163, 10.1074/jbc.M202653200

HK Bayele, 2006, Cis and trans regulation of hepcidin expression by upstream stimulatory factor., Blood, 108, 4237, 10.1182/blood-2005-07-027037

G Nicolas, 2002, The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation., J Clin Invest, 110, 1037, 10.1172/JCI0215686

RH Wenger, 2002, Cellular adaptation to hypoxia: O₂-sensing protein hydroxylases, hypoxia-inducible transcription factors, and O₂-regulated gene expression., FASEB J, 16, 1151, 10.1096/fj.01-0944rev

WG Kaelin Jr, 2008, Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway., Mol Cell, 30, 393, 10.1016/j.molcel.2008.04.009

GL Semenza, 2007, Hypoxia-inducible factor 1 (HIF-1) pathway., Sci STKE, 2007, cm8, 10.1126/stke.4072007cm8

C Peyssonnaux, 2007, Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs)., J Clin Invest, 117, 1926, 10.1172/JCI31370

C Warnecke, 2008, The specific contribution of hypoxia-inducible factor-2α to hypoxic gene expression in vitro is limited and modulated by cell type-specific and exogenous factors., Exp Cell Res, 314, 2016, 10.1016/j.yexcr.2008.03.003

HM Sowter, 2003, Predominant role of hypoxia-inducible transcription factor (Hif)-1α <italic>versus</italic> Hif-2α in regulation of the transcriptional response to hypoxia., Cancer Res, 63, 6130

C Warnecke, 2004, Differentiating the functional role of hypoxia-inducible factor (HIF)-1α and HIF-2α (EPAS-1) by the use of RNA interference: erythropoietin is a HIF-2α target gene in Hep3B and Kelly cells., FASEB J, 18, 1462, 10.1096/fj.04-1640fje

T Rothhammer, 2005, Bone morphogenic proteins are overexpressed in malignant melanoma and promote cell invasion and migration., Cancer Res, 65, 448, 10.1158/0008-5472.448.65.2

SM Elbashir, 2002, Analysis of gene function in somatic mammalian cells using small interfering RNAs., Methods, 26, 199, 10.1016/S1046-2023(02)00023-3

J Wang, 2004, Iron-mediated degradation of IRP2, an unexpected pathway involving a 2-oxoglutarate-dependent oxygenase activity., Mol Cell Biol, 24, 954, 10.1128/MCB.24.3.954-965.2004

SI Tazuke, 1998, Hypoxia stimulates insulin-like growth factor binding protein 1 (IGFBP-1) gene expression in HepG2 cells: a possible model for IGFBP-1 expression in fetal hypoxia., Proc Natl Acad Sci U S A, 95, 10188, 10.1073/pnas.95.17.10188

JG Scharf, 2005, Oxygen-dependent modulation of insulin-like growth factor binding protein biosynthesis in primary cultures of rat hepatocytes., Endocrinology, 146, 5433, 10.1210/en.2005-0948

AJ Belanger, 2002, Hypoxia up-regulates expression of peroxisome proliferator-activated receptor gamma angiopoietin-related gene (PGAR) in cardiomyocytes: role of hypoxia inducible factor 1α., J Mol Cell Cardiol, 34, 765, 10.1006/jmcc.2002.2021

K Cartharius, 2005, MatInspector and beyond: promoter analysis based on transcription factor binding sites., Bioinformatics, 21, 2933, 10.1093/bioinformatics/bti473

JL Babitt, 2007, Modulation of bone morphogenetic protein signaling in vivo regulates systemic iron balance., J Clin Invest, 117, 1933, 10.1172/JCI31342

E Nemeth, 2003, Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein., Blood, 101, 2461, 10.1182/blood-2002-10-3235

RH Wang, 2005, A role of SMAD4 in iron metabolism through the positive regulation of hepcidin expression., Cell Metab, 2, 399, 10.1016/j.cmet.2005.10.010

MV Verga Falzacappa, 2008, A bone morphogenetic protein (BMP)-responsive element in the hepcidin promoter controls HFE2-mediated hepatic hepcidin expression and its response to IL-6 in cultured cells., J Mol Med, 86, 531, 10.1007/s00109-008-0313-7

A Calzolari, 2006, TfR2 localizes in lipid raft domains and is released in exosomes to activate signal transduction along the MAPK pathway., J Cell Sci, 119, 4486, 10.1242/jcs.03228

T Goswami, 2006, Hereditary hemochromatosis protein, HFE, interaction with transferrin receptor 2 suggests a molecular mechanism for mammalian iron sensing., J Biol Chem, 281, 28494, 10.1074/jbc.C600197200

J Gao, 2009, Interaction of the hereditary hemochromatosis protein HFE with transferrin receptor 2 is required for transferrin-induced hepcidin expression., Cell Metab, 9, 217, 10.1016/j.cmet.2009.01.010

B Andriopoulos Jr, 2009, BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism., Nat Genet, 41, 482, 10.1038/ng.335

D Meynard, 2009, Lack of the bone morphogenetic protein BMP6 induces massive iron overload., Nat Genet, 41, 478, 10.1038/ng.320

B Courselaud, 2004, Strain and gender modulate hepatic hepcidin 1 and 2 mRNA expression in mice., Blood Cells Mol Dis, 32, 283, 10.1016/j.bcmd.2003.11.003

GG Braliou, 2008, 2-Oxoglutarate-dependent oxygenases control hepcidin gene expression., J Hepatol, 48, 801, 10.1016/j.jhep.2007.12.021

SO Choi, 2007, ROS mediate the hypoxic repression of the hepcidin gene by inhibiting C/EBPα and STAT-3., Biochem Biophys Res Commun, 356, 312, 10.1016/j.bbrc.2007.02.137

DR Ashby, 2009, Plasma hepcidin levels are elevated but responsive to erythropoietin therapy in renal disease., Kidney Int, 75, 976, 10.1038/ki.2009.21

M Mastrogiannaki, 2009, HIF-2α, but not HIF-1α, promotes iron absorption in mice., J Clin Invest, 119, 1159, 10.1172/JCI38499

M Vokurka, 2006, Hepcidin mRNA levels in mouse liver respond to inhibition of erythropoiesis., Physiol Res, 55, 667, 10.33549/physiolres.930841

M Pak, 2006, Suppression of hepcidin during anemia requires erythropoietic activity., Blood, 108, 3730, 10.1182/blood-2006-06-028787

D Meynard, 2009, Lack of the bone morphogenetic protein BMP6 induces massive iron overload., Nat Genet, 41, 478, 10.1038/ng.320

B Andriopoulos Jr, 2009, BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism., Nat Genet, 41, 482, 10.1038/ng.335

DR Ashby, 2009, Erythropoietin administration in humans causes a marked and prolonged reduction in circulating hepcidin., Haematologica

JP Pinto, 2008, Erythropoietin mediates hepcidin expression in hepatocytes through EPOR signalling and regulation of C/EBPα., Blood, 111, 5727, 10.1182/blood-2007-08-106195