| Project/Area Number |
14082206
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Aichi Medical University |
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Principal Investigator |
KIMATA Koji Aichi Medical University, Institute medical Science, Professor (10022641)
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| Co-Investigator(Kenkyū-buntansha) |
HABUCHI Osami Aichi University, Education, Professor (90024067)
HABUCHI Hiroko Aichi Medical University, Institute for medical, Assistant Professor (90329821)
NAGAI Naoko Aichi Medical University, Institute for medical Science, Research Associate (00367799)
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| Project Period (FY) |
2002 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥179,000,000 (Direct Cost: ¥179,000,000)
Fiscal Year 2006: ¥35,500,000 (Direct Cost: ¥35,500,000)
Fiscal Year 2005: ¥35,500,000 (Direct Cost: ¥35,500,000)
Fiscal Year 2004: ¥36,000,000 (Direct Cost: ¥36,000,000)
Fiscal Year 2003: ¥36,000,000 (Direct Cost: ¥36,000,000)
Fiscal Year 2002: ¥36,000,000 (Direct Cost: ¥36,000,000)
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| Keywords | Heparan sulfate / Cell growth factors / Morphogen / Concentration gradient / Chondroitin sulfate / Proteoglycans / Glycosaminoglycans / Mutant mouse / 形態形成因子(モルフォゲン) / コンドロイチン / 細胞外マトリックス |
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| Research Abstract |
Heparan sulfate (HS) whose basic backbone structure consists of repeating disaccharide of glucuronosyl glucosamine has astronomical number of different structures by sulfation at different positions and by isomerization of glucuronosyl residue. HS usually locates on the cell surfaces and in the extracellular matrix and its structure alters in a spacio-temporal manner. Most of secretary and soluble cell growth factors, cytokines and morphogens which are well known to be required for important cell activities such as cell proliferation, cell differentiation and cell morphology, for example, FGF and Wnt, have properties to bind to HS. Therefore, we hypothesized that those factors, when they differ, may bind to the HS portions with different structures specifically so that each activity of those factors could be regulated by HS distinctively. In this study we first clarified that different factors actually bind to HS with different O-sulfation positions. We then subjected moue, chicken, Zebrafish, and Drosophila to the alteration of genes for HS O-sulfation enzymes, and observed apparent abnormality of organogenesis and tissue-morphogensis in those animals. We further provided some evidence to show that the observed abnormality was due to altered signalings of those factors which were caused, by the abnormal changes in HS structure. Taken together, our study revealed the occurrence of regulation mechanisms of the activities of cell growth factors and morphogens by HS chains.
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