Regulation of Hepcidin and Iron-Overload Disease

Annual Review of Pathology: Mechanisms of Disease - Tập 4 Số 1 - Trang 489-515 - 2009
Pauline L. Lee1, Ernest Beutler1
1Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037

Tóm tắt

Hepcidin, a 25-amino-acid antimicrobial peptide, is the central regulator of iron homeostasis. Hepcidin transcription is upregulated by inflammatory cytokines, iron, and bone morphogenetic proteins and is downregulated by iron deficiency, ineffective erythropoiesis, and hypoxia. The iron transporter ferroportin is the cognate receptor of hepcidin and is destroyed as a result of interaction with the peptide. Except for inherited defects of ferroportin and hepcidin itself, all forms of iron-storage disease appear to arise from hepcidin dysregulation. Studies using multiple approaches have begun to delineate the molecular mechanisms that regulate hepcidin expression, particularly at the transcriptional level. Knowledge of the regulation of hepcidin by inflammation, iron, erythropoiesis, and hypoxia will lead to an understanding of the pathogenesis of primary hemochromatosis, secondary iron overload, and anemia of inflammatory disease.

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Tài liệu tham khảo

10.1074/jbc.M008922200

10.1016/S0014-5793(00)01920-7

10.1111/j.0105-2896.2004.0124.x

10.1172/JCI0215686

10.1182/blood-2002-10-3235

10.1074/jbc.M008923200

10.1073/pnas.151179498

10.1182/blood-2006-02-003376

10.1073/pnas.072632499

10.1038/ng1053

10.1182/blood-2003-07-2524

10.1182/blood-2005-05-2049

10.1091/mbc.e07-01-0060

10.1126/science.1104742

10.1093/hmg/ddg225

10.1038/sj.ejhg.5201490

10.1016/j.bcmd.2007.07.009

10.1016/j.bcmd.2007.07.010

10.1182/blood-2003-10-3366

10.1016/j.jhep.2005.02.047

10.1182/blood.V70.3.757.757

10.1016/j.bcmd.2003.11.003

10.1016/j.bcmd.2007.02.004

10.7326/0003-4819-133-5-200009050-00008

10.1016/S0140-6736(02)07447-0

10.1056/NEJMoa041534

10.1007/BF01606062

Valberg LS, 1975, J. Lab. Clin. Med., 86, 479

10.1093/ajcp/63.2.179

10.1182/blood.V74.2.844.844

Acton RT, 2006, Ethn. Dis., 16, 815

10.1086/302318

10.1016/S1079-9796(03)00041-X

10.1006/bcmd.2002.0586

10.1182/blood-2003-09-3358

10.1186/gb-2007-8-10-r221

10.1182/blood-2003-09-3300

10.1038/ng2059

10.1038/ng1150

10.1016/S0140-6736(03)12602-5

10.1182/blood-2007-06-096503

10.1016/j.bcmd.2007.10.001

10.1152/ajpgi.00092.2006

10.1111/j.1365-2141.2004.05044.x

10.1073/pnas.0403108101

10.1038/75534

10.1182/blood.V97.9.2555

10.1111/j.1365-2141.2004.04950.x

10.3324/haematol.11942

Majore S, 2006, Haematologica, 91, ECR33

10.1182/blood-2004-08-3042

10.1073/pnas.162360699

10.1182/blood-2004-04-1416

10.1136/gut.2004.062018

10.1046/j.1365-2141.2002.03509.x

10.1182/blood-2004-12-4844

10.1159/000089479

10.1111/j.1399-0004.2008.01017.x

10.1182/blood-2004-01-0072

Wallace DF, 2005, Haematologica, 90, 254

10.1182/blood-2004-01-0192

10.1038/ng1274

10.1016/j.bcmd.2005.02.001

10.1111/j.1399-0004.2005.00413.x

10.3324/haematol.11247

10.1016/0002-9343(87)90175-6

10.1016/j.jhep.2005.06.024

10.1016/j.bcmd.2004.05.001

10.1006/bcmd.2000.0271

10.3324/haematol.10701

10.1111/j.1365-2141.2004.05165.x

10.1182/blood-2004-01-0400

10.1182/blood-2006-08-041004

10.1172/JCI25049

10.1172/JCI25683

10.3324/haematol.10545

10.1182/blood-2004-01-0332

10.1111/j.0009-9163.2004.00254.x

10.1016/j.febslet.2007.02.002

10.1016/j.bcmd.2003.08.003

10.1172/JCI200113468

10.1038/90038

De Domenico I, 2006, Haematologica, 91, 92

10.1182/blood-2005-02-0561

10.1016/j.bcmd.2004.12.002

10.1016/j.bcmd.2007.03.008

10.1016/S1079-9796(03)00165-7

10.1016/S1079-9796(03)00164-5

10.1182/blood-2007-01-066068

10.1242/dev.01081

10.1242/dev.01342

10.1182/blood-2005-03-1159

10.1172/JCI200420945

10.1182/blood-2004-08-3375

10.1182/blood-2002-04-1260

Ganz T, 2002, Isr. Med. Assoc. J., 4, 1043

10.1172/JCI21441

10.1038/ncpneph0655

10.1556/APhysiol.94.2007.1-2.9

10.1097/01.mib.0000235097.86360.04

10.1182/blood.V71.4.1124.1124

Weatherall DJ, 2006, Williams Hematology, 633

10.1038/nm1629

10.1128/MCB.20.10.3742-3751.2000

10.3324/haematol.10842

De FL, 2006, Haematologica, 91, 1336

10.1182/blood-2006-06-027631

10.1038/ng1777

10.1074/jbc.M608788200

10.1242/jcs.03074

10.1074/jbc.M503511200

Huang FW, 2005, Blood, 106, 153a, 10.1182/blood.V106.11.153.153

10.1016/j.cmet.2005.10.010

10.1182/blood-2005-05-1845

10.1016/j.bcmd.2007.06.023

10.1182/blood-2007-07-100677

10.1172/JCI31342

10.1073/pnas.0603124103

10.1182/blood-2007-04-087593

10.1111/j.1365-2141.2007.06728.x

10.1074/jbc.M202653200

10.1182/blood-2002-11-3610

10.1182/blood-2004-06-2477

10.1182/blood-2004-06-2481

10.1074/jbc.C600197200

10.1091/mbc.e06-09-0798

10.1074/jbc.M706720200

10.1182/blood.V108.11.1539.1539

10.1182/blood-2007-05-091108

10.1006/bcmd.2002.0573

10.1182/blood-2006-06-028787

Vokurka M, 2006, Physiol. Res., 55, 667, 10.33549/physiolres.930841

10.7326/0003-4819-55-1-103

Kattamis A, 2006, Haematologica, 91, 809

10.1182/blood-2004-06-2422

Sun XF, 2006, Zhongguo Shi Yan Xue Ye Xue Za Zhi, 14, 778

Flanagan JM, 2005, Blood, 106, 999a, 10.1182/blood.V106.11.3584.3584

10.1016/j.bbrc.2007.02.137

Semenza GL, 2007, Sci. STKE., 407, cm8

10.1172/JCI31370

10.1126/science.1157121