2007 Fiscal Year Final Research Report Summary
Targeting oxidative stress and new therapy in metabolic syndrome
| Project/Area Number |
17209034
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
FUJITA Toshiro The University of Tokyo, Faculty of Medicine, Professor (10114125)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Katsutoshi The University of Tokyo, Faculty of Medicine, Associa Professor (00292863)
ISSHIKI Masashi The University of Tokyo, Faculty of Medicine, Associa Professor (70302734)
ANDO Katsuyuki The University of Tokyo, Faculty of Medicine, Associa Professor (60184313)
SHIMOSAWA Tatsuo The University of Tokyo, Faculty of Medicine, Lecturer (90231365)
NAGASE Miki The University of Tokyo, Faculty of Medicine, Associa Professor (60302733)
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| Project Period (FY) |
2005 – 2007
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| Keywords | Oxidative stress / Organ regeneration / Metabolic syndrome / aldosterone / inflammation / salt / adrenomedullin |
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| Research Abstract |
In the present study, we have investigated new therapeutic approaches to metabolic syndrome. We have focused on the role of salt, aldosterone, inflammation, and adrenomedullin in relation to oxidative stress and seek new targets to reduce oxidative stress and thus protect organs from damages. In addition, we investigated possible therapeutic approaches to induce organ regenerations and new genes in metabolic model rats. We revealed that orally loaded salt increases ROS and aggravates insulin resistance, and cardiac function. Adrenomedullin has been reported as an intrinsic antioxidants and its deficiency induces metabolic syndrome. Mac-1 is expressed on leukocyte and plays an important role in leukocyte adherence and vascular damages. Using Local Shwartzman Reaction model, we revealed role of Mac-1 in vasculitis and possible therapeutic target in preventing vascular damages in metabolic syndrome where local vascular inflammation could be one pathogenesis. To induce organ regeneration i
… More
s a promising therapeutic tool and in renal damages, we focused on side population cell as a multipotent stem cells in the kidney. Using several renal impairment models, we revealed that cytokines induce side population cell apoptosis and suppresses organ regeneration. Aldosterone blockade, angiotensin II blockade as well as epigenetical regulation by trichostatin A could rescue side population cells in damaged kidney. Finally we investigated possible genetical locus in metabolic syndrome model rat and found responsible locus on chromosome 3, 4 and 12. Among them, mutation in kynurenine aminotransferase-1 links body weight, blood pressure, NEFA synthesis and insulin resistance in rat model. In conclusion, the present research project revealed several new insights in therapeutic target in metabolic syndrome. The importance of oxidative stress and aldosterone as well as epigenetical regulations and new gene are all play pivotal role in pathogenesis of metabolic syndrome and related organ damages. There are several possible compounds are now available that lead us to a new era in treating metabolic syndrome. Less
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Research Products
(34 results)
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[Journal Article] Leukemia inhibitory factor induces multi-lineage differentiation of adult stem-like cells in kidney via kidney-specific cadherin 16.2005
Author(s)
Hishikawa K, Marumo T, Miura S, Nakanishi A, Matsuzaki Y, Shibata K, Kohike H, Komori T, Hayashi M, Nakaki T, Nakauchi H, Okano H, Fujjita T
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Journal Title
Biochem Biophys Res Commun 328
Pages: 288-291
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Expression and regulation of adrenomedullin in renal glomerular podocytes.2005
Author(s)
Hino M, Nagase M, Kaname S, Shibata S, Nagase T, Oba S, Funaki M, Kobayashi N, Kawachi H, Mundel P, Fujita T
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Journal Title
Biochem Biophys Res Commun 330
Pages: 178-185
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Musculin/Myor is expressed in kidney side population cells and regulate their function.2005
Author(s)
Hishikawa K, Marumo T, Miura S, Nakanishi A, Matsuzaki Y, Shibata K, Ichiyanagi T, Kohike H, Komori T, Takahashi I, Takase O, Imai N, Yoshikawa M, Inowa T, Hayashi M, Nakauchi H, Okano H, Fujita T
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Journal Title
J. Cell Biol 169
Pages: 921-928
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Leukemia inhibitory factor induces multi-lineage differentiation of adult stem-like cells in kidney via kidney-specific cadherin 162005
Author(s)
Hishikawa K, Marumo T, Miura S, Nakanishi A, Matsuzaki Y, Shibata K, Kohike H, Komori T, Hayashi M, Nakaki T, Nakauchi H, Okano H, Fujjita T.
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Journal Title
Biochem Biophys Res Commun 328
Pages: 288-291
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Expression and regulation of adrenomedullin in renal glomerular podocytes2005
Author(s)
Hino M, Nagase M, Kaname S, Shibata S, Nagase T, Oba S, Funaki M, Kobayashi N, Kawachi H, Mundel P, Fujita T.
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Journal Title
Biochem Biophys Res Commun 330
Pages: 178-185
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Musculin/Myor is expressed in kidney side population cells and regulate their function2005
Author(s)
Hishikawa K, Marumo T, Miura S, Nakanishi A, Matsuzaki Y, Shibata K, Ichiyanagi T, Kohike H, Komori T, Takahashi I, Takase O, Imai N, Yoshikawa M, Inowa T, Hayashi M, Nakauchi H, Okano H, Fujita T.
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Journal Title
J Cell Biol 169
Pages: 921-928
Description
「研究成果報告書概要(欧文)」より
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