13A060506 ﾌ 6ﾑ8ｦﾐ04ｦﾐ ﾒ ﾌ08 6ﾑ80304ｦﾐ ﾞ026ﾑ806 ﾌ03ｦ ﾌ6ｾ4 6ﾑ86 706 6ｧ90709: 08 02000702030602fi0ｹ0 030ｸ703000604026ｧ80ｹ0 000002 6 50803060400086ｦ0 02080ｸ7 0406 6ｧ803080ｸ7 ｦﾌ. 09 apple 09000ｷ303096ｧ9080ｸ7, 09. ﾌ06020807fi00080ｸ7 ﾞ00 09 06 06 020306026ｧ8 ﾒ03060706026ｧ8 ﾞ0905, 03080408020800006ｧ908 ｰｦﾐappleapple0802030702000608 ｱ, 05000404 0308076ｧ90209 Papageorgiou V, Ikonomou M. Hepcidin: the principal regulator of iron metabolism. A Paed. Department A.U.TH., ｰIppokration ｱ General Hospital, Thessaloniki,.Greece. Paediatr N Gr 2010, 22: 264-270. 0900036ｧ903096 709. ﾇ 006 706 6ｧ90709 apple08020003006ｧ9 020807 02000702030602fi 030ｸ703000604026ｧ8 02090ｹ0 08000806fi0402 04090ｹ0 02080ｸ7 0406 6ｧ803080ｸ7 02 06 00apple06apple03 閨0807 02 02 閨040006 0001 閨04080ｸ704 03 閨0409 04020907 apple 030809 閨070006 02090ｹ0 07 06006ｧ9 0ｹ0 040308076ｧ9 0ｹ0 07fi04080ｸ7. 0903fi- 02000602 06 0906 0006 080300fi0709 apple080ｸ7 apple 0307090002 06 applefi 02 09apple 0208026ｦ00202-03 02 06 09 閨02020306046ｧ8 02090ｹ0 0001 03020702 06 applefi 020907 apple0804fi020902 02080ｸ7 020ｸ7-020308080803086ｦ00702 0406 6ｧ803080ｸ7, 0209 080300090008076ｧ8, 020907 0ｸ7apple08016ｧ9 02 06 020907 00030ｸ7030308apple0806090206026ｧ8 03 0402090306fi020902 02080ｸ7 080309 07060400086ｦ0. 6ｾ400 0008-0306 02fi 00apple6ｧ9apple00 08 09 006 706 6ｧ90709 03 000400006ｦ0080702 0ｹ0 0209 0800030308apple0803-026ｧ90709, 09 08apple086ｧ9 006ｧ907 06 0ｸ7apple006ｦ0030ｸ70709 0906 020907 applefi 080409 02080ｸ7 0406 6ｧ8-03080ｸ7 applefi 020807 0007 08020ｸ7020207030608 04060308 apple03080ｹ0 0209 040ｸ704020900 0206026ｧ8 020ｸ7-0203080808036ｧ9. ﾌ0ｸ70406 0402060207, 09 006 706 6ｧ90709 0000apple08 6ｧ9ｨB0006 020907 閨0108 08 02080ｸ7 0406 6ｧ803080ｸ7 applefi 0803060400 閨07 026ｦ00202 03 fiapple0ｷ30ｹ0 02 000702000308026ｦ00202 03, 02 09apple 0208026ｦ00202 03 02 06 02 00 020308080709. 0304080ｸ707 apple030802 03006ｧ9 閨0ｷ30ｹ0 046ｧ8000003 0607080803000ｹ0 000309 0402090306 02 閨0ｹ0 00 閨0308 0806 0906 020807 apple030804-060803060400fi 020ｷ307 00apple06apple 陦0ｷ307 02090ｹ0 006 706 6ｧ907090ｹ0, 030307 02 006ｧ9 00 閨0308 080ｹ0 0007 閨040006 000604 0403006ｧ9 02 06 02 030600030ｷ303006ｧ9 04020907 0203060706026ｧ8 apple03070109 02fi- 00. 08apple070304080ｸ707, apple080303 閨0ｹ0 000003030807020602 閨0ｹ0 apple030808apple020602 閨0ｹ0 0906 07 閨080ｸ70ｹ0 06 09070ｷ304020602086ｦ00ｹ0 02 06 030003 apple000ｸ7020602086ｦ00ｹ0 040208apple086ｦ00ｹ0 fi040807 08080307 0403 閨070006000ｹ0 apple080ｸ7 040400026ｧ9ｨB080702 06 0000 0208 000002 6 50803060400fi 02080ｸ7 0406 6ｧ803080ｸ7. 閨0100060ｹ0-02030006 0607: 006 706 6ｧ90709, 046ｧ9 0903080ｹ0, 0800030308apple0803026ｧ90709, 07 06006ｧ9 040308076ｧ9 0ｹ0 07fi04080ｸ7. Abstract. Hepcidin is the principal regulator of iron metabolism and simultaneously acts as the key-regulator of anemia of chronic disease. It is a hormone which is produced by the hepatocytes and its production is triggered mainly by the amount of circulating body iron, inflammation, hypoxia and the erythropoietic activity of the body. In molecular level, hepcidin acts via the binding of ferroportin which is the basic cellular exporter of iron from the intracellular space to the systemic circulation. The exact role of hepcidin is the inhibition of iron cellular efflux. Several laboratory methods for hepcidin ｯs quantification have already been proposed but none has been established for clinical use so far. Hepcidin could open new horizons concerning diagnosis and therapy of diseases related to iron metabolism. Key words: hepcidin, iron, ferroportin, anemia of chronic disease. E0604 090ｷ3096ｧ8 ｦ 020003000ｸ702 6ｧ9 閨0209 閨040006 04090000060ｷ303006ｧ9 000009070309 apple03fi08 080ｹ0 040209 000003 閨0209 02090ｹ0 08000806fi0402 04090ｹ0 02080ｸ7 0406 6ｧ803080ｸ7 02 06 02090ｹ0 apple 030809-070006 0ｹ0 02090ｹ0 07 06006ｧ9 0ｹ0 040308076ｧ9 0ｹ0 07fi04080ｸ7. ﾇ 006 706 6ｧ90709 03000ｷ303006ｧ9-02 06 046ｧ8000003 08 02000702030602fi0ｹ0 030ｸ703000604026ｧ80ｹ0 02080ｸ7 000002 6 50803060400086ｦ0 02080ｸ7 0406 6ｧ803080ｸ7 02 06 6 5 040602fi0ｹ0 0000040803 6 509026ｧ80ｹ0 02080ｸ7 07080408apple080609020602086ｦ0 040ｸ704026ｧ800 02080ｹ01,2. 0903fi02000602 06 0906 0006 000602036ｧ8 apple030ｷ3-02000ｹ10709 apple080ｸ7 apple08020003006ｧ902 06 applefi 00fi03060ｹ0 25 0006070801 陦 02 06 040ｸ7-07026ｧ9030002 06 applefi 02 09apple 0208026ｦ00202 03 3. ﾇ 046ｦ0070300046ｧ8 02090ｹ0 00apple07-090002 06 applefi 020907 0ｸ7apple000300apple0703020006 02080ｸ7 080309 07060400086ｦ0 0400 046ｧ9 09-0308 02 06 applefi 0209 080300090008076ｧ8, 000706 0003 020206070002 06 0400 040ｸ707036ｧ8-02000ｹ0 閨07020807090ｹ0 00030ｸ7030308apple0806090206026ｧ80ｹ0 03 0402090306fi020902 0ｹ0. ﾇ 07-09070603060409 02090ｹ0 006 706 6ｧ907090ｹ0 02 06 02080ｸ7 040900 07020602086ｦ0 02090ｹ0 03fi03080ｸ7 040208 000002 6 50803060400fi 02080ｸ7 0406 6ｧ803080ｸ7 03 00apple0803086ｦ00400 0000030308-0702060207 07 07086ｧ9010006 07 閨080ｸ70ｹ0 03fi00080ｸ70ｹ0 040209 030003 apple006ｧ9 02090ｹ0 0406-090308apple000706026ｧ80ｹ0 07 06006ｧ9 0ｹ0, 02090ｹ0 06000804030ｷ30007020ｷ304090ｹ0 02 06 02090ｹ0 07 06006ｧ9 0ｹ0 040308076ｧ9 0ｹ0 07fi04080ｸ74,5.
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O06 Nicolas 02 06 040ｸ707. 0000 060207 02080ｸ70ｹ0 apple0006030700 02 02 02 閨030901 07 fi0206 09 006 706 6ｧ90709 0003 020206070006 020907 apple03fi0403096 709 0406 6ｧ803080ｸ7 applefi 0208 閨0702000308 02 06 apple 030703030903 00000606070006 020907 apple08 閨0400000ｸ7046ｧ8 02080ｸ7 applefi 02 00-020308080709 15. 6ｾ400 00080306 02fi 00apple6ｧ9apple00 08, 09 006 706 6ｧ90709 030ｸ703006ｧ9ｨB0006 0209 000002 08080307 02080ｸ7 Fe 00 閨040ｷ3 02090ｹ0 閨0400000ｸ704090ｹ0 02090ｹ0 0800030308apple0803026ｧ907090ｹ0, 02090ｹ0 06 0000006 503 0706026ｧ80ｹ0 apple030ｷ302000ｹ107090ｹ0 apple080ｸ7 apple08 6ｧ9-0006 0208 Fe applefi 0208 00040ｷ30200030602fi 020ｷ307 020ｸ7020207030ｷ307 apple03080ｹ0 020907 020ｸ70203080808036ｧ9. ﾇ 0800030308apple0803026ｧ90709 6 5036ｧ904020002 06 0402 00apple060309-0306 0207 026ｦ00202 03 02080ｸ7 0ｷ3 0002 02026ｦ003080ｸ7, 0402 00 0203080807-09, 0402 09apple 0208026ｦ00202 03 02 06 0402 026ｦ00202 03 02080ｸ7 apple03 02086ｦ0-0702 16. 0002 07 09 006 706 6ｧ90709 040ｸ707 0003006ｧ9 0000 0209 0800030308apple0803026ｧ90709, (0400 閨07 040ｸ709020002030600 閨0708 040900006ｧ908 046ｦ007 0004090ｹ0 apple080ｸ7 02 03006ｧ902 06 Hepcidin-Binding Domain, HBD) 17 090006080ｸ70309006ｧ902 06 閨07 046ｦ000apple03080208 0208 08apple086ｧ908 0007 08020ｸ7020206070002 06 02 06 08 0909006ｧ9 020003060207 0400 apple08 fi00090409 02090ｹ0 0800030308apple0803026ｧ907090ｹ018,19. ﾇ 00030702020ｷ30409 02090ｹ0 0800030308apple0803026ｧ907090ｹ0 08 0909006ｧ9 0400 00060203fi02000309 apple0003000ｸ703-030ｷ30409 02080ｸ7 Fe applefi 02 026ｦ00202 03 apple03080ｹ0 0208 apple03070400 (6ﾑ80602. 2). ｦ 08 09apple 0208026ｦ00202 0308 006ｧ907 06 0ｸ702fi apple080ｸ7 03000602080ｸ70309006ｧ9 0ｷ30ｹ0 000ｸ7 6ｧ9-
13CM YK CM YK 266 09 06 06 020306026ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 22, 3 T84 N terminus H74 R75 S76 K77 C78 G79 M80 C81 C82 K83 T61 D60 C73 C72 G71 C70 C69 F68 I67 C66 I65 F63 H62 P64 6ﾑ80602. 1. 0408006ｧ8 apple00apple0206 6ｧ9080ｸ7 006 706 6ｧ907090ｹ0. 04030902080ｹ0 ｰ 06040309026ｧ803 0ｹ0 0406 6ｧ803080ｸ7 ｱ (iron-sensor) 02 06 fi02 07 02 00apple6ｧ9apple00 02080ｸ7 080309 07060400086ｦ0 0400 046ｧ9 090308 006ｧ907 06 0ｸ7010900 閨07 040208 09apple 0208026ｦ00202 0308, 0000 0006 0400060307 apple08036ｦ0apple0308020ｷ307 000904 0706-04000607 02 06 0303090300apple06 030704000ｷ307 (apple080ｸ7 0007 閨04080ｸ707 06000ｸ70203060706-0403006ｧ9 apple036ｧ8030ｷ30ｹ0 02fi0009), apple030802 03006ｧ902 06 6ｦ001090409 02090ｹ0 006 706 6ｧ907090ｹ0. 6ｾ40900 07020602fi 03fi0308 04020907 apple 03 090ｷ3096ｧ8 02090ｹ0 08 6ｧ9070002 06 07 apple 6ｧ9ｨB0006 09 GPI-linked hemojuvelin (HJV), 09 ｦﾌ0906 (Bone Morphogenic Protein), 09 HFE, o TfR1 02 06 TfR2 20-24. 0900 0209 040ｸ700-00000208046ｧ8 0ｸ7020607, 0208 09apple 0208026ｦ00202 0308 000700030908apple0806006ｧ902 06, 010002060707 0208 00080708apple070206 02090ｹ0 000002 090ｷ3096ｧ80ｹ0 046ｧ800 02080ｹ0 0007 08020ｸ70202070306 0000 0209 040ｸ70000000208046ｧ8 020ｷ307 apple030ｷ302000ｸ8070607 SMAD 25 02 06 apple030802 03006ｧ902 06 0200-03060207 09 閨020803 0409 02080ｸ7 apple00apple0206 6ｧ9080ｸ7 02090ｹ0 006 706 6ｧ907090ｹ0 (6ﾑ80602. 3). M00-02 0303070100060ｹ0 0402080ｸ70ｹ0 apple 03 apple07070ｷ3 0ｸ7apple08 0804006ｧ90ｹ0 (HJV, TfR2, HFE) 08 0909086ｦ007 0400 04 000903 閨0ｹ0 020600 閨0ｹ0 006 706 6ｧ907090ｹ0 02 06, 0ｸ702080007020ｷ30ｹ0, 0400 02 02 0402070400060ｹ0 0000 0ｸ7apple000308fi03020ｷ30409 02080ｸ7 080309 07060400086ｦ0 0400 046ｧ9-090308 ( 06000804030ｷ30007020ｷ30409) 26,27. 6ﾑ86 706 6ｧ90709 02 06 020309030807080006026ｧ8 06000804030ｷ30007020ｷ30409 ﾇ 020309030807080006026ｧ8 06000804030ｷ30007020ｷ30409 006ｧ907 06 07fi04080ｹ0 apple080ｸ7 04-03 020209036ｧ9ｨB0002 06 applefi 0ｸ7010900 閨0709 000702000306026ｧ8 apple080303fi08090409 02080ｸ7 Fe 02 06 000002 鐶pple000602 0007 applefi03000409 02080ｸ7 000002070303080ｸ7 0402080ｸ70ｹ0 060402086ｦ00ｹ0. ﾌ 0203fiapple080ｹ0 02030903080708000602fi020902 0ｹ0 006ｧ907 06 040ｸ7076ｧ8030ｷ30ｹ0 0ｸ70208040ｷ30006-02fi0ｹ0 0ｸ7apple08030006applefi000007080ｹ0 02 06 04apple 076ｧ90ｷ30ｹ0 0ｸ70208040ｷ3000602fi0ｹ0 (00apple060203-026ｧ80ｹ0) 28. ﾇ 020309030807080006026ｧ8 06000804030ｷ30007020ｷ30409 040ｷ3036ｧ9ｨB0002 06 0400 0607080803080ｸ70ｹ0 026ｦ0apple080ｸ70ｹ0 0707030809 0000 0209 000002070303 0109 02080ｸ7 09080706-6ｧ9080ｸ7 apple080ｸ7 apple030802 03006ｧ9 0209 07fi0408. ﾇ apple0608 020806076ｧ8 08080307 0209 0000-02070303 0109 02080ｸ7 09080706 6ｧ9080ｸ7 HFE (C282Y 000002070303 0109) 29 apple080ｸ7 00 0307ｨB0002 06 040208 04030ｷ300fi040ｷ300 6 30. ﾞ04030007006ｧ90ｹ0 0000 0208 000002 03-03 0900 閨0708 0908076ｧ9 0608 閨04080ｸ707 04 00090307 00apple6ｧ9apple00 006 706 6ｧ907090ｹ0, apple030709-00 0208 08apple086ｧ908 02 02 000602076ｦ00006 0209 040ｸ70404 閨02060409 02080ｸ7 HFE 0000 0209 046ｦ00703000409 02090ｹ0 006 706 6ｧ907090ｹ0. 01 00090307 00apple6ｧ9apple00 006 706 6ｧ907090ｹ0 apple0308-02 03086ｦ007 0ｸ76 7090307 00apple6ｧ9apple00 0800030308apple0803026ｧ907090ｹ0 04020907 020ｸ70202 0306026ｧ8 0000006 503070709, 0000 apple0802 閨03000400 020907 0ｸ7010900 閨0709 000702000306026ｧ8 apple0803- A) 0ﾊ3ｦﾐｦﾁｦﾑ B) 0ﾊ3ｦﾐｦﾁｦﾑ ｦ ｦﾗｦﾉｦﾄ0ﾋ7ｦﾍｦﾇ ｦ ｦﾗｦﾉｦﾄ0ﾋ7ｦﾍｦﾇ Fe Fe Fe-Tf ｦﾅｦﾍｦﾓｦﾅｦﾑｦﾏｦﾊ0ﾌ3ｦﾓｦﾓｦﾁｦﾑｦﾏ Fe Fe-Tf ｦﾅｦﾍｦﾓｦﾅｦﾑｦﾏｦﾊ0ﾌ3ｦﾓｦﾓｦﾁｦﾑｦﾏ ｦﾌｦﾁｦﾊｦﾑｦﾏｦﾕ0ﾋ4ｦﾃｦﾏ ｦﾌｦﾁｦﾊｦﾑｦﾏｦﾕ0ﾋ4ｦﾃｦﾏ ｦﾕｦﾅｦﾑｦﾑｦﾏｦﾐｦﾏｦﾑｦﾓ0ﾋ7ｦﾍｦﾇ ｦﾕｦﾅｦﾑｦﾑｦﾏｦﾐｦﾏｦﾑｦﾓ0ﾋ7ｦﾍｦﾇ 6ﾑ80602. 2. 090904 07060400fi0ｹ0 030704090ｹ0 006 706 6ｧ907090ｹ0 0400 020ｸ70202 030602fi 00apple6ｧ9apple00 08. A) 6ｾ400 040ｸ707036ｧ802000ｹ0 00apple0703020006 0ｹ0 0406 6ｧ803080ｸ7 00apple07090002 06 09 046ｦ00703000409 006 706 6ｧ907090ｹ0 applefi 02 09apple 0208026ｦ00202 03, B) ﾇ 006 706 6ｧ90709 04020804006ｦ00006 040209 0800030308apple0803026ｧ90709 000702000308020ｸ7020207030ｷ307 02 06 00 0203080807090ｷ307 0000apple08 6ｧ9ｨB080702 0ｹ0 020907 閨0108 08 02080ｸ7 0406 6ｧ803080ｸ7. CM YK CM YK
13CM YK CM YK 09 06 06 020306026ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 22, 3 267 03fi08090409 Fe 02 06 020907 0ｸ7010900 閨0709 apple0003000ｸ703 閨030ｷ30409 0406 6ｧ803080ｸ7 applefi 02 00 020308080709. 6ｾ4apple 0706fi020003000ｹ0 00080308 閨0ｹ0 020309030807080006026ｧ80ｹ0 06000804030ｷ30007020ｷ304090ｹ0 080803086ｦ007 000002 0303070100060ｹ0 09080706 6ｧ90ｷ307 HJV, TfR2 02 06 006 706 6ｧ907090ｹ0 (HAMP) 31,32. 6ｾ4020907 020309030807080006026ｧ8 06-000804030ｷ30007020ｷ30409 02 00apple6ｧ9apple00 02090ｹ0 006 706 6ｧ907090ｹ0 006ｧ907 06 0003 02020ｷ300-07, 0700010703020902 applefi 020807 026ｦ0apple08 02090ｹ0 000002070303 01090ｹ0. 6ﾑ801 6ｧ90300-0409 apple08020003006ｧ9 08 026ｦ0apple080ｹ0 apple080ｸ7 0808006ｧ9030002 06 0400 000002070303 0109 02080ｸ7 09080706 6ｧ9080ｸ7 02090ｹ0 0800030308apple0803026ｧ907090ｹ0, fiapple080ｸ7 09 006 706 6ｧ90709 00apple0803006ｧ9 07 006ｧ907 06 02 06 0ｸ7010900 閨0709, 06fi0206 apple03fi02000602 06 080ｸ70406 0402060207 0906 07026ｧ9-0402 0409 02080ｸ7 0ｸ7apple08 0804 陦 02090ｹ0 0800030308apple0803026ｧ907090ｹ0 040209 03070409 02090ｹ0 02 06 03000602080ｸ7030906026ｧ8 0700apple0703020006 02090ｹ0 080300fi07090ｹ033-35. 6ﾑ803 02020ｷ300 閨0709 閨020803 0409 006 706 6ｧ907090ｹ0, 02 06 閨00000004 09apple - 0206026ｧ8 0406 6ｧ8030ｷ30409, 0ｸ7apple0703040006 00apple6ｧ904090ｹ0 0400 apple0803080ｸ7036ｧ9000ｹ0, 030208-080306026ｧ8 09apple 0208apple07030006 02 06 03086ｧ9000ｷ30109 0000 HCV 36. 6ﾑ86 706 6ｧ90709 02 06 080300090008076ｧ8 ﾇ 006 706 6ｧ90709 0007 apple08020003006ｧ9 00fi0708 030ｸ703000604026ｧ8 02080ｸ7 0406 6ｧ803080ｸ7, 030307 02 06 040900 07020602fi 040ｸ707 00020602fi apple 030709080702 000002 016ｦ0 02090ｹ0 07000ｸ707 0ｹ0 02080ｸ7 080309 07060400086ｦ0 02 06 02080ｸ7 000002 6 50803060400086ｦ0 02080ｸ7 0406-6ｧ803080ｸ737. 03020406, 02 00apple6ｧ9apple00 02090ｹ0 006 706 6ｧ907090ｹ0 006ｧ907 06 0ｸ7010900-07 0400 apple00036ｧ9apple020ｷ30409 03086ｧ9000ｷ301090ｹ0. 6ｾ4020907 apple030802000600 閨0709 apple00036ｧ9- apple020ｷ30409 09 6ｦ001090409 02090ｹ0 apple 03 090ｷ3096ｧ80ｹ0 02090ｹ0 080300fi07090ｹ0 096ｧ9070002 06 0000 000904 07060400086ｦ00ｹ0 apple080ｸ7 00 040400026ｧ9ｨB080702 06 0000 02 00apple6ｧ9apple00 0406-6ｧ803080ｸ7 040208 6ｧ900, 000706 09 IL-6 08 6ｧ9070002 06 07 apple 6ｧ9ｨB0006 6 5 040602fi 03fi0308 040209 036ｦ00300060409 02090ｹ0 apple 03 090ｷ3096ｧ80ｹ0 02090ｹ038. 6ｾ40ｸ709020002030600 閨07, 09 IL-6 000700030908apple0806006ｧ9 020907 閨020803 0409 02080ｸ7 apple00apple0206 6ｧ9080ｸ7 02090ｹ0 006 706 6ｧ907090ｹ039 (6ﾑ80602. 3). ﾇ 046ｦ00703000409 02090ｹ0 00-6 706 6ｧ907090ｹ0 02 0207 020907 0801006ｧ9 03086ｧ9000ｷ30109 096ｧ9070002 06 000702fi0ｹ0 08036ｧ9090ｷ307 0ｷ3030607 (6 0603000ｹ0), 08applefi0200 03 00apple0803086ｦ00400 07 04 03 02020903060402006ｧ9 02 06 0ｷ30ｹ0 apple030ｷ302000ｹ10709 0801006ｧ9 0ｹ0 080704090ｹ0. ﾇ 6ｦ001090409 02090ｹ0 006 706 6ｧ907090ｹ0 040209 03086ｧ9000ｷ30109 04020804006ｦ00006 040209 00006ｧ90ｷ30409 02090ｹ0 040ｸ7070803060207 apple - 030004fi000007090ｹ0 apple0804fi020902 0ｹ0 0406 6ｧ803080ｸ7 040208 030806000809fi0708 apple 0307-09080702 40,41. ﾞ6ｦ001090409 02090ｹ0 006 706 6ｧ907090ｹ0 040ｸ7006 5 6ｧ9070006 fi0406 00fi0708 0400 0801006ｧ9000ｹ0 030307 02 06 0400 0403fi0706000ｹ0 0803000900080706 00060ｹ0 02 02 0402070400060ｹ0 ｨC 07 06006ｧ9 040308076ｧ9 0ｹ0 07fi04080ｸ7ｨC (0403fi0706000ｹ0 03080600060100060ｹ0, 02 03026ｧ9-07080ｹ0, 06 02 03 04 閨0ｹ0 07080408apple080609020602086ｦ0) 42-45. ﾒ 02 040208036ｧ8 02090ｹ0 006 706 6ｧ907090ｹ0 applefi 020907 07 06006ｧ9-0ｸ7apple08016ｧ9 ﾇ apple 03 090ｷ3096ｧ8 02090ｹ0 006 706 6ｧ907090ｹ0 applefi 02 09apple 0208026ｦ00202 03 030ｸ703-006ｧ9ｨB0002 06 00apple6ｧ904090ｹ0 applefi 020907 07 06006ｧ9 02 06 020907 0ｸ7apple08016ｧ9 2, 0806 08apple086ｧ9-000ｹ0 apple030802 03086ｦ007 00006ｧ90ｷ30409 02090ｹ0 006 706 6ｧ907090ｹ0 06040200 07 0303006ｧ9 09 07 0402 030206026ｧ8 02090ｹ0 00apple6ｧ9 03 0409 04020907 000702000306026ｧ8 apple080303fi0809-0409 Fe 02 06 02 0ｸ702fi04030807 07 000ｸ708 0803006ｧ9 09 apple0003000ｸ703 閨030ｷ30409 02080ｸ7 Fe applefi 02 00 020308080709 02 06 02 09apple 0208026ｦ00202 03. 0900 020807 0203fiapple08 0ｸ702fi apple0003060404fi020003080ｹ0 046ｧ9 0903080ｹ0 03 006ｧ907 06 06-03 閨040600080ｹ0 0906 020907 0ｸ7010900 閨0709 00030ｸ7030308apple086ｧ9090409, 06fi0206, fiapple0ｷ30ｹ0 006ｧ907 06 09070ｷ30402fi, 0400 02 02 0402070400060ｹ0 0ｸ7apple08016ｧ9 0ｹ0 apple 0602086ｦ00702 06 apple00-03060404fi020003 00030ｸ7030307 0600080408 6ｧ90306 0906 020907 0207030ｸ76 709 020ｷ307 07 09020607 02080ｸ7 080309 07060400086ｦ0. 6ｾ400 00080306 02fi 00apple6ｧ9apple00 08 0400 02-02 0402070400060ｹ0 0ｸ7apple08016ｧ9 0ｹ0 08 HIF (Hypoxia Inducible Factor) 08 6ｧ9070002 06 07 02 02 閨040006 040900 07020602fi 03fi0308 040209 036ｦ00300060409 020ｷ307 0303 090607 apple080ｸ7 040ｸ7006 5 6ｧ907080ｸ707, 040ｸ704020900 02060207 6ｧ8 0007 08020ｸ702-02070306, 06040200 07 00apple0602000ｸ70403006ｧ9 07000004 apple0802 02070402 0409 02090ｹ0 080ｸ704060803080906026ｧ80ｹ0 08010ｸ709fi070ｷ304090ｹ0 02080ｸ7 080309 07060400086ｦ0. 6ｾ40ｸ7090200-02030600 閨07, apple03fi02000602 06 0906 046ｦ007080308 000002 0903 0806020607 apple 03-09fi07020ｷ307 apple080ｸ7 apple03080709080ｸ707 020907 閨020803 0409 02090ｹ0 00030ｸ7030308apple080609-026ｧ907090ｹ0, 02090ｹ0 0203 0704080003036ｧ907090ｹ0 02 06 02080ｸ7 0ｸ7apple08 0804 陦 0203 07-04080003036ｧ907090ｹ0, 000706 02 02 0402 閨0303080ｸ707 020907 閨020803 0409 02080ｸ7 09080706-6ｧ9080ｸ7 02090ｹ0 006 706 6ｧ907090ｹ0. 6ﾑ8apple0800 閨070ｷ30ｹ0, 08 HIF 02 0ｸ702080403fi070ｷ30ｹ0 ) 000700030908apple0806006ｧ9 020907 00030ｸ7030308apple086ｧ9090409 02 06 6 5) apple030807090006 020907 0ｸ7-010900 閨0709 06 0300040600fi020902 02080ｸ7 Fe 46. 6ｾ46ｦ000080ｷ307 0000 apple03fi- ｦｴｦﾗｦﾇｦﾋ0ﾋ4 ｦﾅｦﾐ0ﾋ7ｦﾐｦﾅｦﾄｦﾁ Fe ｦｴｦﾐｦﾏｦﾎ0ﾋ7ｦﾁ ｦｶｦﾁｦﾌｦﾇｦﾋ0ﾋ4 ｦﾅｦﾐ0ﾋ7ｦﾐｦﾅｦﾄｦﾁ Fe ｦ ｦﾍｦﾁｦﾉｦﾌ0ﾋ7ｦﾁ ｦｧｦﾐｦﾁｦﾓｦﾏｦﾊ0ﾌ3ｦﾓｦﾓｦﾁｦﾑｦﾏ ｦ ｦﾑｦﾔｦﾈｦﾑｦﾏｦﾐｦﾏ0ﾋ7ｦﾇｦﾒｦﾇ SMAD STAT3 ERK1/2 + HAMP ｨC IL-6 ｦｫｦﾏ0ﾋ7ｦﾌｦﾘｦﾎｦﾇ ｦｵｦﾋｦﾅｦﾃｦﾌｦﾏｦﾍ0ﾋ6 6ﾑ80602. 3. 09080708apple070206 0007 08020ｸ70202070306 0ｹ0 00apple 090ｷ3096ｧ80ｹ0 046ｧ800 02080ｹ0 040208 09apple 0208026ｦ00202 0308 0906 020907 apple 03 090ｷ3096ｧ8 02090ｹ0 006 706 6ｧ907090ｹ0. 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Nemeth E, Ganz T. Regulation of iron metabolism by hepcidin. Ann Rev Nutr 2006, 26: 323-42. 2. Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood 2003, 102: 783-8. 3. Bergamaschi G, Villani L. Serum hepcidin: a novel diagnostic tool in disorders of iron metabolism. Haematologica 2009, 94: 1631-3. 4. Pak M, Lopez M, Garayan V, Ganz T, Rivera S. Suppression of hepcidin during anemia requires erythropoietic activity. Blood 2006, 108: 3730-5. 5. 09070902 03090ｹ0 罍ﾞ. ﾞ0600 02080308096ｧ9 04020907 0203060706026ｧ8 apple03070109. ｦﾐ 02030602 閨0ｹ0 0002- fi0400060ｹ0 09.01. 09 0404 036ｧ9 09, 2008, 223-37. 6. Park C, Valore E, Waring A, Ganz T. Hepcidin, a urinary antimicrobial peptide synhtesized in the liver. J Biol Chem 2001, 276: 7806-10. 7. Krause A, Neitz S, Magert HJ, Schultz A, Forssmann W, Schulz-Knappe P, et al. LEAP-1 a novel highly disulfidebonded human peptide, excibits antimicrobial activity. FEBS Lett 2000, 480: 147-50. 8. Kemna E, Tjalsma H, Willems H, Swinkels D. Hepcidin from discovery to differential diagnosis. Haematologica 2008, 93: 90-7. 9. Lee P, Beutler E. Regulation of hepcidin and iron-overload disease. Annu Rev Pathol 2009, 4: 489-515. 10. 6ｾ4 fi0909080ｸ7 ｦ, 縺000ｷ30309086ｦ00309 6ﾑ8, ﾒfi04040ｸ76 5. 6ﾑ86 706 6ｧ90709 02 06 000002 6 508-03060400fi0ｹ0 02080ｸ7 0406 6ｧ803080ｸ7. 09 06 06 020306026ｧ8 2009, 72: 413-22. 11. Munoz M, Villar I, Garcia-Erce J. An update on iron physiology. World J Gastroenterol 2009, 15: 4617-26. 12. Donovan A, Bownlie A, Zhou Y, Shepard J, Pratt SJ, Moynihan J, et al. Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter. Nature 2000, 403: 776-81. 13. Zhang A, Enns C. Molecular mechanisms of normal iron homeostasis. Hematology 2009, 2009: 207-14.
1309 06 06 020306026ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 22, 3 269 14. Pigeon C, Ilyin G, Courselaud B, et al. A new mouse liverspecific gene encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem 2001, 276: 7811-9. 15. Nicolas G, Bennoun M, Devaux I, et al. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc Natl Acad Sci USA 2001, 98: 8780-5. 16. Abboud S, Haile D. A novel mammalian iron-regulated protein involved in intracellular iron metabolism. J Biol Chem 2000, 275: 19906-12. 17. De Domenico I, Nemeth E, Nelson J, Phillips J, Ajioka R, Kay M, et al. The hepcidin binding site on ferroportin is evolutionarily conserved. Cell Metab 2008, 8: 146-56. 18. Nemeth E, Tuttle M, Powelson J, Vaughn M, Donovan A, Ward D, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 2004, 306: 2090-3. 19. Ramey G, Deschemin J, Durel B, Canonne-Hergaux F, Nicolas G, Vaulout S. Hepcidin targets ferroportin for degradation in hepatocytes. Haematologica 2010, 95: 501-4. 20. ﾆhang A, Yang F, Wang J, Tsukamoto H, Enns C. Hemojuvelin-neogemin interaction is required for bone morphogenic protein-4 induced hepcidin expression. J Biol Chem 2009, 284: 22580-9. 21. 09eynard J, Kautz L, Darnaud V, Canonne-Hergaux F, Coppin H, Roth M. Lack of the bone morphogenetic protein BMP6 induces massive iron overload. Nat Genet 2009, 41: 478-81. 22. Alexander J, Kowdley K. HFE-associated hereditary hemochromatosis. Genet Med 2009, 11: 307-13. 23. Graham R, Chua A, Herbison C, Olynyk J, Trinder D. Liver iron transport. World J Gastroenterol 2007, 13: 4725-36. 24. Fleming R. Iron sensing as a partnership: HFE and transferrin receptor 2. Cell Metab 2009, 9: 211-2. 25. Darshan D, Anderson G. Interacting signals in the control of hepcidin expression. Biometals 2009, 22: 77-87. 26. Weiss G. Genetic mechanisms and modifying factors in hereditary hemochromatosis. Nat Rev Gastroenterol Hepatol 2010, 7: 50-8. 27. Gehre S, Pietrangelo A, Kascak M, Braner A, Eisold M, Kulaksiz H, et al. HJV gene mutation in European patients with juvenile hemochromatosis. Clin Genet 2005, 67: 425-8. 28. Janssen M. Hereditary haemochromatosis. Neth J Med 2007, 65: 409-10. 29. Beutler E. Hemochromatosis: genetics and pathophysiology. Annu Rev Med 2006, 57: 331-47. 30. Le Gac G, Ferec C. The molecular genetic of haemochromatosis. Eur J Hum Genet 2005, 13: 1172-85. 31. Pietrangelo A. Hereditary hemochromatosis: pathogenesis, diagnosis, and treatment. Gastroenterology 2010, 139: 393-408. 32. Rideau A, Mangeat B, Matthes T, Trono D, Beris P. Molecular mechanism of hepcidin deficiency in a patient with juvenile hemochromatosis. Haematologica 2007, 92: 127-8. 33. Gamaschella C, Poggiali E. Rare types of genetic hemochromatosis. Acta Haematol 2009, 122: 140-5. 34. Fernandez A, Preza G, Phung Y, De Domenico I, Kaplan J, Ganz T, et al. The molecular basis of hepcidin-resistant hereditary hemochromatosis. Blood 2009, 114: 437-43. 35. Ajioka R, Phillips J, Weiss R, Dunn D, Smit M, Proll S, et al. Down regulation of hepcidin in porphyria cutanea tarda. Blood 2008, 112: 4723-8. 36. Kohgo Y, Ikuta K, Ohtake T, Torimoto Y, Kato J. Iron o- verload and cofactors with special reference to alcohol, hepatitis C virus infection and steatosis/insulin resistance. World J Gastroenterol 2007, 13: 4699-706. 37. Wessling-Resnick M. Iron homeostasis and the inflammatory response. Annu Rev Nutr 2010, 30: 105-22. 38. Deicher R, Horl W. New insights into the regulation of iron homeostasis. Eur J Clin Invest 2006, 36: 301-9. 39. Nicolas G, Chauvet C, Viatte L, Danan J, Bigard X, Devaux I, et al. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia and inflammation. J Clin I west 2002, 110: 1037-44. 40. Ganz T. Iron in innate immunity: starve the invaders. Curr Opin Immunol 2009, 21: 63-7. 41. Rivera S, Nemeth E, Gabayan V, Lopez M, Farshidi D, Ganz T. Synthetic hepcidin causes rapid dose-dependent hypoferremia and is concentrated in ferroportin-containing organs. Blood 2005, 106: 2196-9. 42. Weiss G. Iron metabolism in the anemia of chronic disease. Biochim Biophys Acta 2009, 1790: 682-93. 43. Chen J, Chloupkova M. Abnormal iron uptake and liver cancer. Cancer Biol Ther 2009, 8: 1699-708. 44. Grotto H. Anaemia of cancer: an overview of mechanisms involved in its pathogenesis. Med Oncol 2008, 25: 12-21. 45. Balla J, Jeney V, Varga Z, Komodi E, Nagy E, Balla G. Iron homeostasis in chronic inflammation. Acta Physiol Hung 2007, 94: 95-106. 46. Smith T, Robbins P, Ratcliffe P. The human side of hypoxiainducible factor. Br J Haematol 2008, 141: 325-34. 47. Pinto J, Ribeiro S, Pontes H, Thowfeequ S, Tosh D, Carvalho F, Porto G. Erythropoietin mediates hepcidin expression in hepatocytes through EPOR signaling and regulation of C/EBPa. Blood 2008, 111: 5727-33. 48. Tanno T, Bhanu N, Oneal P, Goh S, Staker P, Lee Y, et al. High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. Nat Med 2007,13: 1096-101. 49. Kulaksiz H, Gehrke S, Janetzko A, Rost D, Bruckner T, Kallinowski B,et al. Pro-hepcidin: expression and cell-specific localisation in the liver and its regulation in hereditary haemochromatosis, chronic renal insufficiency and renal anaemia. Gut 2004, 53: 735-43. 50. Swinkels D, Girelli D, Laarakkers C, Kroot J, Campostrini N, Kemna E, et al. Advances in quantitative hepcidin measurments by time-of-flight mass spectrometry. PloS ONE 2008, 3: e2706. 51. Bansal S, Halket J, Bomford A, Simpson R, Vasavda N, Thein S, et al. Quantitation of hepcidin in human urine by liquid
13270 09 06 06 020306026ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 22, 3 chromatography-mass spectrometry. Anal Biochem 2009, 384: 245-53. 52. Ganz T, Olbina G, Girelli D, Nemeth E, Westerman M. Immunoassay for human serum hepcidin. Blood 2008, 112: 4292-7. 53. Kemna E, Tjalsma H, Podust V, Swinkels D. Mass spectometry-based hepcidin measurments in serum and urine: analytical aspects and clinical implications. Clin Chem 2007, 53: 620-8. 54. Piperno A, Mariani R, Trombini P, Girelli D. Hepcidin modulation in human diseases: from research to clinic. World J Gastroenterol 2009, 15: 538-51. 55. Ganz T. Hepcidin and its role in regulating systemic iron metabolism. Hematology Am Soc Educ Program 2006, 29-35: 507. ﾞ03030903080903 086ｧ9 : ｦﾌ. 09 apple 09000ｷ303096ｧ9080ｸ7 0909020308applefi03000ｷ30ｹ0 109 546 22 05000404 0308076ｧ90209 ｦ 0903: 2310 263351 E-mail: valiapap@yahoo.com Correspondence auth08r: V. Papageorgiou Mitropoleos 109 546 22 Thessaloniki, Greece Tel: 2310 263351 E-mail: valiapap@yahoo.com