Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs)

被引：512

作者：

Peyssonnaux, Carole

Zinkernagel, Annelies S.

Schuepbach, Reto A.

Rankin, Erinn

Vaulont, Sophie

Haase, Volker H.

Nizet, Victor ^{[1
]}

Johnson, Randall S.

机构：

[1] Univ Calif San Diego, Sch Med, Div Biol Sci, Mol Biol Sect, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 USA

[3] Scripps Res Inst, Dept Immunol, La Jolla, CA USA

[4] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA

[5] Univ Paris 05, CNRS, UMR 8104, Inst Cochin, Paris, France

[6] INSERM, U567, Paris, France

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2007年 / 117卷 / 07期

关键词：

D O I：

10.1172/JCI31370

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Iron is essential for many biological processes, including oxygen delivery, and its supply is tightly regulated. Hepcidin, a small peptide synthesized in the liver, is a key regulator of iron absorption and homeostasis in mammals. Hepcidin production is increased by iron overload and decreased by anemia and hypoxia; but the molecular mechanisms that govern the hepcidin response to these stimuli are not known. Here we establish that the von Hippel-Lindau/hypoxia-inducible transcription factor (VHL/HIF) pathway is an essential link between iron homeostasis and hepcidin regulation in vivo. Through coordinate downregulation of hepcidin and upregulation of erythropoietin and ferroportin, the VHL-HIF pathway mobilizes iron to support erythrocyte production.

引用

收藏

页码：1926 / 1932

页数：7

相关论文

共 33 条

[1] A novel mammalian iron-regulated protein involved in intracellular iron metabolism [J].

Abboud, S ;

Haile, DJ .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (26) :19906-19912

[2] Disruption of oxygen homeostasis underlies congenital Chuvash polycythemia [J].

Ang, SO ;

Chen, H ;

Hirota, K ;

Gordeuk, VR ;

Jelinek, J ;

Guan, YL ;

Liu, EL ;

Sergueeva, AI ;

Miasnikova, GY ;

Mole, D ;

Maxwell, PH ;

Stockton, DW ;

Semenza, GL ;

Prchal, JT .

NATURE GENETICS, 2002, 32 (04) :614-621

[3] Effect of cell-cell interactions in preservation of cellular phenotype: cocultivation of hepatocytes and nonparenchymal cells [J].

Bhatia, SN ;

Balis, UJ ;

Yarmush, ML ;

Toner, M .

FASEB JOURNAL, 1999, 13 (14) :1883-1900

[4]

BRUGNARA C, 1994, J LAB CLIN MED, V123, P660

[5] Transcriptional repression of human cad gene by hypoxia inducible factor-1α [J].

Chen, KF ;

Lai, YY ;

Sun, HS ;

Tsai, SJ .

NUCLEIC ACIDS RESEARCH, 2005, 33 (16) :5190-5198

[6] A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1 alpha regulates the VEGF expression and is potentially involved in lung and vascular development [J].

Ema, M ;

Taya, S ;

Yokotani, N ;

Sogawa, K ;

Matsuda, Y ;

FujiiKuriyama, Y .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (09) :4273-4278

[7] A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis [J].

Feder, JN ;

Gnirke, A ;

Thomas, W ;

Tsuchihashi, Z ;

Ruddy, DA ;

Basava, A ;

Dormishian, F ;

Domingo, R ;

Ellis, MC ;

Fullan, A ;

Hinton, LM ;

Jones, NL ;

Kimmel, BE ;

Kronmal, GS ;

Lauer, P ;

Lee, VK ;

Loeb, DB ;

Mapa, FA ;

McClelland, E ;

Meyer, NC ;

Mintier, GA ;

Moeller, N ;

Moore, T ;

Morikang, E ;

Prass, CE ;

Quintana, L ;

Starnes, SM ;

Schatzman, RC ;

Brunke, KJ ;

Drayna, DT ;

Risch, NJ ;

Bacon, BR ;

Wolff, RK .

NATURE GENETICS, 1996, 13 (04) :399-408

[8]

FINCH C, 1994, BLOOD, V84, P1697

[9] HRF, a putative basic helix-loop-helix-PAS-domain transcription factor is closely related to hypoxia-inducible factor-1 alpha and developmentally expressed in blood vessels [J].

Flamme, I ;

Frohlich, T ;

vonReutern, M ;

Kappel, A ;

Damert, A ;

Risau, W .

MECHANISMS OF DEVELOPMENT, 1997, 63 (01) :51-60

[10] Hepcidin expression inversely correlates with the expression of duodenal iron transporters and iron absorption in rats [J].

Frazer, DM ;

Wilkins, SJ ;

Becker, EM ;

Vulpe, CD ;

McKie, AT ;

Trinder, D ;

Anderson, GJ .

GASTROENTEROLOGY, 2002, 123 (03) :835-844

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