Regulatory mechanisms of hepcidin, the central regulator of body iron homeostasis

• Project/Area Number: 22591033
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Kyoto University
• Principal Investigator: KAWABATA Hiroshi 京都大学, 医学研究科, 講師 (10329401)
• Co-Investigator(Renkei-kenkyūsha): TOMOSUGI Naohisa 金沢医科大学, 総合医学研究所, 教授 (80155580) ; MORI Kiyoshi 京都大学, 医学研究科, 准教授 (60343232)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 鉄代謝 / ヘプシジン / フェリチン / 造血幹細胞移植 / GVHD / 鉄過剰症 / 血液内科学

Research Abstract

The purpose of this study was to clarify the pathogenesis of iron disorders through basic and clinical studies of iron metabolism-associated molecules such as hepcidin and ferritin. We identified that hepcidin expression by hepatoma cells was affected by microenvironmental pH. We also found that iron storage protein H-ferritin was selectively taken up by erythroid cells through transferrin receptor 1. Furthermore, we demonstrated that pre-transplant hyperferritinemia was a risk factor for bacterial infection and disease relapse after allogenic stem cell transplantation.

Research Products

• [Journal Article] Differing impacts of pretransplant serum ferritin and c-reactive protein levels on the incidence of chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation (2013)
  • Author(s): Sakamoto S, Kawabata H, Kanda J, Uchiyama T, Mizumoto C, Kondo T, Yamashita K, Ichinohe T, Ishikawa T, Kadowaki N, Takaori-Kondo A
  • Journal Title: Int J Hematol Volume: 97 Issue: 1 Pages: 109-116
  • DOI: 10.1007/s12185-012-1229-0
  • NAID: 10031144642
  • Peer Reviewed
• [Journal Article] 鉄代謝のバイオマーカー<検査指標3>ヘプシジン (2012)
  • Author(s): 川端浩
  • Journal Title: 臨床検査 Volume: 56 Pages: 1064-1069
• [Journal Article] 鉄センサーの分子機構 (2012)
  • Author(s): 川端浩
  • Journal Title: 細胞(1346-7557) Volume: 44 Pages: 187-190
• [Journal Article] Acidic milieu augments the expression of hepcidin, the central regulator of iron homeostasis (2012)
  • Author(s): Mizumoto C, Kawabata H, Uchiyama T, Sakamoto S, Kanda J, Tomosugi N, Takaori-Kondo A
  • Journal Title: Int J Hematol Volume: 96 Issue: 6 Pages: 701-709
  • DOI: 10.1007/s12185-012-1223-6
  • NAID: 10031144608
  • Peer Reviewed
• [Journal Article] A case of congenital dyserythropoietic anemia type 1 in a japanese adult with a cdan1 gene mutation and an inappropriately low serum hepcidin-25 level (2012)
  • Author(s): Kawabata H, Doisaki S, Okamoto A, Uchiyama T, Sakamoto S, Hama A, Hosoda K, Fujikura J, Kanno H, Fujii H, Tomosugi N, Nakao K, Kojima S, Takaori-Kondo A
  • Journal Title: Intern Med Volume: 51 Pages: 917-920
  • NAID: 130002061879
  • Peer Reviewed
• [Journal Article] Transferrin receptor 2 による鉄代謝シグナル (2012)
  • Author(s): 川端浩
  • Journal Title: 臨床血液(0485-1439) Volume: 52 Pages: 399-405
  • Peer Reviewed
• [Journal Article] A case of congenital dyserythropoietic anemia type 1 in a japanese adult with a cdan1 gene mutation and an inappropriately low serum hepcidin-25 level. (2012)
  • Author(s): Kawabata H, Doisaki S, Okamoto A, Uchiyama T, Sakamoto S, Hama A, Hosoda K, Fujikura J, Kanno H, Fujii H, Tomosugi N, Nakao K, Kojima S, Takaori-Kondo A
  • Journal Title: Intern Med Volume: 51 Pages: 917-920
  • NAID: 130002061879
  • Peer Reviewed
• [Journal Article] バイオマーカーとしてのフェリチン (2011)
  • Author(s): 諫田淳也, 川端浩
  • Journal Title: 血液フロンティア Volume: 21 Pages: 75-84
• [Journal Article] ヘプシジン(hepcidin)-そのがん性貧血における意義 (2011)
  • Author(s): 川端浩
  • Journal Title: 癌と化学療法(0385-0684) Volume: 25 Pages: 603-608
• [Journal Article] Pretransplant serum ferritin and c-reactive protein as predictive factors for early bacterial infection after allogeneic hematopoietic cell transplantation (2011)
  • Author(s): Kanda J, Mizumoto C, Ichinohe T, Kawabata H, Saito T, Yamashita K, Kondo T, Takakura S, Ichiyama S, Uchiyama T, Ishikawa T
  • Journal Title: Bone Marrow Transplant Volume: 46 Issue: 2 Pages: 208-216
  • DOI: 10.1038/bmt.2010.108
  • Peer Reviewed
• [Journal Article] Iron overload and allogeneic hematopoietic stem-cell transplantation (2011)
  • Author(s): Kanda J, Kawabata H, Chao NJ
  • Journal Title: Expert Rev Hematol Volume: 4 Issue: 1 Pages: 71-80
  • DOI: 10.1586/ehm.10.81
  • Peer Reviewed
• [Journal Article] Transferrin Receptor 2による鉄代謝シグナル (2011)
  • Author(s): 川端浩
  • Journal Title: 臨床血液 Volume: 52 Pages: 399-405
  • Peer Reviewed
• [Journal Article] Iron overload and allogeneic hematopoietic stem-cell transplantation. (2011)
  • Author(s): Kanda J, Kawabata H, Chap NJ
  • Journal Title: Expert Rev Hematol. Volume: 4 Pages: 71-80
  • Peer Reviewed
• [Journal Article] Pretransplant serum ferritin and c-reactive protein as predictive factors for early bacterial infection after allogeneic hematopoietic cell transplantation. (2011)
  • Author(s): Kanda J, Mizumoto C, Ichinohe T, Kawabata H, Saito T, Yamashita K, Kondo T., Takakura S, Ichiyama S, Uchiyama T, Ishikawa T
  • Journal Title: Bone Marrow Transplant. Volume: 46 Pages: 208-216
  • Peer Reviewed
• [Journal Article] 鉄過剰症と造血器腫瘍の予後 (2010)
  • Author(s): 川端浩, 諫田淳也, 石川隆之
  • Journal Title: 血液フロンティア Volume: 20 Pages: 1025-1033
• [Journal Article] 炎症性貧血 (2010)
  • Author(s): 川端浩
  • Journal Title: 感染・炎症・免疫 Volume: 40 Pages: 291-293
• [Journal Article] 鉄代謝の分子機構 (2010)
  • Author(s): 川端浩
  • Journal Title: 日本内科学会雑誌 Volume: 99 Pages: 1173-1179
  • NAID: 10026426216
• [Journal Article] トランスフェリンレセプター2 (2010)
  • Author(s): 川端浩
  • Journal Title: 日本医師会雑誌 Volume: 139 Pages: 330-330
• [Journal Article] 鉄代謝異常と病態 (2010)
  • Author(s): 川端浩
  • Journal Title: 日本検査血液学会雑誌 Volume: 11 Pages: 1-12
  • Peer Reviewed
• [Journal Article] Downregulation of hepcidin resulting from long-term treatment with an anti-il-6 receptor antibody (tocilizumab) improves anemia of inflammation in multicentric castleman's disease (mcd) (2010)
  • Author(s): Song S, N., J., Tomosugi N, Kawabata H, Ishikawa T, Nishikawa T, Yoshizaki K
  • Journal Title: Blood Volume: 116 Issue: 18 Pages: 3627-3634
  • DOI: 10.1182/blood-2010-03-271791
  • Peer Reviewed
• [Journal Article] Downregulation of hepcidin resulting from long-term treatment with an anti-IL-6 receptor antibody (tocilizumab) improves anemia of inflammation in multicentric Castleman's disease (MCD) (2010)
  • Author(s): Song S, N., J., Tomosugi N, Kawabata H, Ishikawa T, Nishikawa, T, Yoshizaki K.
  • Journal Title: Blood Volume: 116 Pages: 3627-3634
  • Peer Reviewed
• [Journal Article] Clinical features and treatments of multicentric castleman's disease: A retrospective study of 21 japanese cases in a single institute
  • Author(s): Kawabata H, Kadowaki N, Nishikori M, Kitawaki T, Kondo T, Ishikawa T, Yoshifuji H, Yamakawa N, Imura Y, Mimori T, Matsumura Y, Miyachi Y, Matsubara T, Haga H, Takaori-Kondo A
  • Journal Title: J Clin Exp Hematopathol in press
  • Peer Reviewed
• [Presentation] 血液疾患における GDF15 と鉄代謝異常(シンポジウム講演) (2012)
  • Author(s): 内山達樹, 川端浩, 友杉直久, 高折晃史
  • Organizer: 第36回日本鉄バイオサイエンス学会学術集会
  • Place of Presentation: 京王プラザホテル札幌・札幌市
  • Year and Date: 2012-09-02
• [Presentation] Transferrin receptor 2による鉄代謝シグナル(シンポジウム) (2011)
  • Author(s): 川端 浩
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜・横浜市
  • Year and Date: 2011-09-25
• [Presentation] キャッスルマン病と炎症性貧血 (2011)
  • Author(s): 川端浩, 諫田淳也, 上田恭典, 友杉直久, 高折晃史
  • Organizer: 第35回日本鉄バイオサイエンス学会学術集会
  • Place of Presentation: 徳島文理大学・徳島市
• [Presentation] Ferritin uptake by human leukocytes and leukemia cell lines(ヒト白血球および白血病細胞株のフェリチン取り込み) (2011)
  • Author(s): Soichiro Sakamoto, Hiroshi Kawabata, Taro Masuda, Tatsuki Uchiyama, Chisaki Mizumoto, Katsuyuki Ohmori and Akifumi Takaori-Kondo
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋国際会議場・名古屋市・愛知県
• [Presentation] Impact of pre-transplant hepcidin-25 in patients undergoing allo-SCT for hematologic malignancies(造血器腫瘍に対する同種造血幹細胞移植における移植前ヘプシジン値の影響) (2011)
  • Author(s): Soichiro Sakamoto, Hiroshi Kawabata, Junya Kanda, Tatsuki Uchiyama, Chisaki Mizumoto, Tadakazu Kondo, Kouhei Yamashita, Tatsuo Ichinohe, Takayuki Ishikawa, Norimitsu Kadowaki, Naohisa Tomosugiand Akifumi Takaori-Kondo
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋国際会議場・名古屋市・愛知県
• [Presentation] 種々の血液疾患における血清 GDF15 値(Serum levels of GDF15 in various hematological disorders) (2011)
  • Author(s): Uchiyama Tatsuki, Kawabata Hiroshi, Kanda Junya, Tomosugi Naohisa, Sakamoto Soichiro, Mizumoto Chisaki, Takaori-Kondo Akifumi
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋国際会議場・名古屋市・愛知県
• [Presentation] PROGNOSTIC IMPACT OF PRE-TRANSPLANT SERUM HEPCIDIN LEVELS ON CLINICAL OUTCOMES AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (2011)
  • Author(s): Soichiro Sakamoto, Hiroshi Kawabata, Junya Kanda, Tatsuki Uchiyama, Chisaki Mizumoto, Tadakazu Kondo, Kouhei Yamashita, Tatsuo Ichinohe, Takayuki Ishikawa, Norimitsu Kadowaki, Naohisa Tomosugi and Akifumi Takaori-Kondo
  • Organizer: 16th Congress of the European Hematology Association
  • Place of Presentation: Excel, London, United Kingdom
• [Presentation] キャッスルマン病と炎症性貧血 (2011)
  • Author(s): 川端浩, 諫田淳也, 上田恭典, 友杉直久, 高折晃史
  • Organizer: 第35回日本鉄バイオサイエンス学会学術集会
  • Place of Presentation: 徳島文理大学・徳島市・徳島県
• [Presentation] Ferritin uptake by human leukocytes and leukemia cell linesヒト白血球および白血病細胞株のフェリチン取り込み (2011)
  • Author(s): Soichiro Sakamoto, Hiroshi Kawabata, Taro Masuda, Tatsuki Uchiyama, Chisaki Mizumoto, Katsuyuki Ohmori, Akifumi Takaori-Kondo
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋国際会議場・名古屋市・愛知県
• [Presentation] Impact of pre-transplant hepcidin-25 in patients undergoing allo-SCT for hematologic malignancies造血器腫瘍に対する同種造血幹細胞移植における移植前ヘプシジン値の影響 (2011)
  • Author(s): Soichiro Sakamoto, Hiroshi Kawabata, Junya Kanda, Tatsuki Uchiyama, Chisaki Mizumoto, Tadakazu Kondo, Kouhei Yamashita, Tatsuo Ichinohe, Takayuki Ishikawa, Norimitsu Kadowaki, Naohisa Tomosugi, Akifumi Takaori-Kondo
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋国際会議場・名古屋市・愛知県
• [Presentation] 種々の血液疾患における血清GDF15値(Serum levels of GDF15 in various hematological disorders) (2011)
  • Author(s): Uchiyama Tatsuki, Kawabata Hiroshi, Kanda Junya, Tomosugi Naohisa, Sakamoto Soichiro, Mizumoto Chisaki, Takaori-Kondo Akifumi
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋国際会議場・名古屋市・愛知県
• [Presentation] Cellular machinery for ferritin uptake (2010)
  • Author(s): Sakamoto S, Mizumoto C, Masuda T, Uchiyama T, Kanda J, Kawabata H
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜・横浜市
  • Year and Date: 2010-09-25
• [Presentation] Transferrin receptor 2による鉄代謝シグナル(シンポジウム) (2010)
  • Author(s): 川端浩
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-25
• [Presentation] Cellular machinery for ferritin uptake. (2010)
  • Author(s): Sakamoto S, Mizumoto C, MasudaT, Uchiyama T, Kanda J, Kawabata H.
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-25
• [Presentation] Impact of Serum Ferritin Levels on the Incidence of Chronic Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation (2010)
  • Author(s): Sakamoto S, Kawabata H, Kanda J, Uchiyama T, Mizumoto C, Kondo T, Ichinohe T, Ishikawa T, Takaori-Kondo A
  • Organizer: The American Society of Hematology 52nd Annual Meeting
  • Place of Presentation: Orland, FL, USA
• [Presentation] Impact of Serum Ferritin Levels on the Incidence of Chronic Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation. (2010)
  • Author(s): Sakamoto S, Kawabata H, Kanda J, Uchiyama T, Mizumoto C, Kondo T, Ichinohe T, Ishikawa T, Takaori-Kondo A.
  • Organizer: The American Society of Hematology 52nd Annual Meeting
  • Place of Presentation: Orland, FL, USA.
• [Presentation] 血液疾患におけるGDF15と鉄代謝異常（シンポジウム講演）
  • Author(s): 内山達樹, 川端浩, 友杉直久, 高折晃史
  • Organizer: 第３６回日本鉄バイオサイエンス学会学術集会
  • Place of Presentation: 札幌市
• [Remarks] ホームページ
• [Remarks] 造血制御研究
  • URL: http://www.kuhp.kyoto-u.ac.jp/~hemonc/research/regulation.html
• [Remarks]
  • URL: http://www.kuhp.kyoto-u.ac.jp/~hemonc/research/regulation.html
• [Remarks]
  • URL: http://www.kuhp.kyoto-u.ac.jp/~hemonc/research/regulation.html