2006 Fiscal Year Final Research Report Summary
In vivo function of versican : Analysis of knockin mice
| Project/Area Number |
17590361
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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 |
Experimental pathology
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| Research Institution | Aichi Medical University |
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Principal Investigator |
WATANABE Hideto Aichi Medical University, Institute for Molecular Science of Medicine, Associate Professor, 分子医科学研究所, 助教授 (90240514)
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| Project Period (FY) |
2005 – 2006
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| Keywords | versican / PG-M / proteoglycan / extracellular matrix / collagen / TGFbeta / BMP |
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| Research Abstract |
We generated knockin mice whose versican lacks the A subdomain of the N-terminal G1 domain. The homozygotes expressed approximately 50% of the mutant versican with decreased incorporation in the extracellular matrix, and showed cardiac dilatation at E9.5 and died by E18.5. In contrast to the complete knockout mice of versican exhibiting severe cardiac malformation, the basic structure of the heart was formed in the kockin homozygotes. Analysis of the heart revealed impaired myocardial cell differentiation with downregulated BMP-signaling, and fibrosis of myocardial wall with up-regulated TGFbeta signaling (submitted).
We investigated the role of versican in mesenchymal condensation of the cartilage primodium, using a chondrogenic cell line N1511, and found that chondroitin sulfate (CS) chains of versican facilitate chondrocyte differentiation (Kiamiya, N., et al., J Biol Chem, 2006).
We analyzed versican present in the articular cartilage, and found that it is in the form of the proteoglycan aggregate with link protein and hyaluronan. CS of versican was much less sulfated than that of aggrecan (Matsumoto, K., et al., J Biol Chem, 2006).
To date, six glycosyltransferases are known to be involved in CS biosynthesis. We attempted to determine the enzyme critical for CS synthesis in cartilage, and found that CS N-acetylgalactosaminyltransferase-1 plays a critical role in the synthesis (Sakai, K., et al., J Biol Chem, 2007).
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