| Project/Area Number |
17591016
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kyoto University |
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Principal Investigator |
KAWABATA Hiroshi Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (10329401)
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| Co-Investigator(Kenkyū-buntansha) |
KAWANAMI Fumitaka Kanazawa Medical University, School of medicine, Assistant Professor, 医学部, 助手 (20350762)
UMEHARA Hisanori Kanazawa Medical University, School of medicine, Professor, 医学部, 教授 (70247881)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | iron metabolism / hepcidin / anemia / hemochromatosis / 鉄代謝 / 炎症性疾患 / マス・スペクトロメトリー |
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| Research Abstract |
The purpose of this study was to clarify the mechanism how iron regulatory molecules (such as HFE, TfR2 and hepcidin) regulate body iron homeostasis and to clarify the clinical significance of this mechanism in malignancies and inflammatory diseases. Hepcidin is a peptide hormone regulating body iron homeostasis and its expression in the liver can be induced by inflammatory cytokine interleukin-6 (IL-6). In collaboration with Dr. Tomosugi (Kanazawa Medical University), we developed a semi-quantitative assay system for serum hepcidin using SELDI-TOF mass-spectrometry (Blood, 2006). Employing this system, we analyzed the level of serum and urine hepcidin in patients with Castleman's disease, a chronic inflammatory disorder with severe anemia, before and after treatment with an anti-IL-6 receptor antibody (Oral presentation at 68^<th> JSH and 48^<th> JSCH at Fukuoka 2006, Oral presentation at BioIron 2007 at Kyoto, Haematologica, in press). We demonstrated that administration of the anti-IL-6 receptor antibody quickly downregulated the levels of serum and urine hepcidin followed by dramatic improvement of inflammatory symptoms as well as microcytic anemia. We are now analyzing the levels of serum and urine hepcidin with this method in a variety of inflammatory and hematopoietic diseases. TfR2 is a molecule that we originally cloned and mutation of this gene has been known to cause hereditary hemochomatosis. We have hypothesized that TfR2 is a sensor of ferric transferrin and can induce expression of hepcidin. Using tetracycline inducible TfR2 expressing systems, we are now trying to clarify the pathway from iron sensing to hepcidin secretion in the liver.
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