2007 Fiscal Year Final Research Report Summary
Heme oxygenase-1 deficiency and failure of human defense mechanisms against generalized chronic inflammation
| Project/Area Number |
17390298
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Kanazawa University |
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Principal Investigator |
KOIZUMI Shoichi Kanazawa University, Graduate School of Medical Science, Professor (50019973)
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| Co-Investigator(Kenkyū-buntansha) |
KASAHARA Yoshihito Kanazawa University, Graduate School of Medical Science, Associate Professor (30204366)
SAIKAWA Yutaka Kanazawa University, Hospital, Lecturer (60283107)
OHTA Kunio Kanazawa University, Hospital, Assistant Professor (00303280)
NIIDA Yo Kanazawa University, Hospital, Lecturer (40293344)
OHTA Kazuhide Kanazawa University, Hospital, Lecturer (20283129)
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| Project Period (FY) |
2005 – 2007
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| Keywords | Heme omenase / Inflammation / Coagulation / fibrinolvsis system / Monnsvts / Endothelial cell / Vasculitis / CD163 / Renal tubular enitherial cell |
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| Research Abstract |
Heme oxygenase (HO) is the rate-limiting enzyme that adds an oxygen molecule to the porphyrin ring of heme, thereby catalyzing the oxidation of heme to biliverdin/ bilirubin, free iron, and carbon monoxide (CO). By producing these metabolites, HO plays a crucial role in humans as a defense factor against a variety of oxidative stresses. The first case of human HO - 1 deficiency was reported by Yachie, et. Al. in our laboratory in 1999. A series of clinical and laboratory investigation of the patient with HO-1 deficiency revealed that (1) The boy completely lacked HO-1, genetically having a two-base-pair deletion in exon 3 of the paternal allele of the gene and a deletion of exon 2 of the maternal allele with genomic exon-deletion (1,730bp) mediated by Alu-Alu, recombination. (2) Dysfunction of both monocytes and endothelial cells was remarkably demonstrated. (2) External continuous stresses triggered excessive systemic inflammatory reactions and marked abnormalities of the coagulation/
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fibrinolysis system, resulting finally in exhaustion of immune and coagulation system. (3) Morphological abnormality of monocytes and significant reduction of their surface molecules resulted in a markedly impaired phagocytosis of monocytes. Furthermore, the selective expansion of a CD16+++, CCR2- subpopulation of monocytes that preferentially produced HO-1 mRNA was shown during the acute phase of infections including both bacterial and viral infections. HO-1 production by alveolar macrophages in childhood pulmonary hypertension correlated with overexpression of CD1G3 surface molecules was also demonstrated. (4) Progressive renal tubulointerstitial injury was remarkable in the patient with HO-1 deficiency. Enhanced production of HO-lin proximal tubular epithelial cells as compared with mesangial cells was shown in variety of renal biopsy specimen as well as in vitro experiment. Recently HO-1 production by urinary tract cells and evaluation of tubulointestinal injury of the kidney was investigated by MA analysis of urinary sediments. Detailed analysis of HO-I deficiency may offer a valuable tool to understand the pathogenesis of and to develop a novel therapeutic approach to systemic inflammatory illnesses. Less
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Research Products
(13 results)
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[Journal Article] Corticosteroid enhances heme oxygenase-I production by circulating monocytes by up-regulating hemoglobin scavenger receptor and amplifying the receptor-mediated uptake of hemoblobin-haptoglobin complex2007
Author(s)
Yamazaki, H., Ohta, K., Tsukiji, H., Toma, T., Hashida, Y., Ishizaki, A., Saito,. T, Arai, S., Koizumi, S., Yachie, A
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Journal Title
Biochem Biophys Res Commun 358(2)
Pages: 506-512
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Glomerular proteinuria induces heme oxygenase-1 gene expression within renal epithelial cells.2005
Author(s)
Shimizu M, Ohta K, Yang Y, Nakai A, Toma T, Saikawa Y, Kasahara Y, Yachie A, Yokoyama H, Seki H, Koizumi S.
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Journal Title
Pediatric Research 58
Pages: 666-671
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Glomerular proteinuria induces heme oxygenase-I gene expression within renal epithelial cells2005
Author(s)
Shimizu, M., Ohta, K., Yang, Y., Nakai, A., Toma, T., Saikawa, Y., Kasahara, Y., Yachie, A., Yokoyama, H., Seki, H., Koizumi, S
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Journal Title
Pediatric Research 58
Pages: 666-671
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Selective expansion of CD16high CCR2- subpopulation of circulating monocytes with preferential production of haem oxygenase (H0)-1 in response to acute inflammation2005
Author(s)
Mizuno, K., Toma, T., Tsukiji, H., Okamoto, H., Yamazaki, H., Ohta, K., Ohta, K., Kasahara, Y., Koizumi, S., Yachie, A
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Journal Title
Clinical and Experimental Immunology 142
Pages: 461-470
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Heme oxygenase (HO)-1 and hematopoiesis : a lesson from the first human case of HO-1 deficiency2007
Author(s)
Koizumi, S., Yachie, A., Kasahara, Y., Saikawa, Y., Niida, Y., Yoma, T., Ohta, Ka., Ohta, Ku
Organizer
36th Annual Scientific Meeting of the ISEH-Society for Hematology and Stem Cells
Place of Presentation
Hamburg, Germany
Year and Date
20070928-30
Description
「研究成果報告書概要(欧文)」より
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[Presentation] HO-1 production by urinary tract cells and evaluation of tubulointerstitial injury of the kidney : immunohistochemical and EIA analysis of urinary sediments2007
Author(s)
Yachie, A., Yokoyama, T., Yuno, T., Ohta, K., Koizumi, S
Organizer
The 5th International Congress Heme Oxygenases 2007
Place of Presentation
Krakow, Poland
Year and Date
20070905-09
Description
「研究成果報告書概要(欧文)」より
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