Regulatory mechanism of chondroitin sulfate expression and glycobiology in disease
Project/Area Number |
16H05088
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Biological pharmacy
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Research Institution | Kobe Pharmaceutical University |
Principal Investigator |
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Research Collaborator |
NADANAKA Satomi
MIKAMI Tadahisa
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Project Period (FY) |
2016-04-01 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2016: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
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Keywords | コンドロイチン硫酸 / プロテオグリカン / グリコサミノグリカン / 神経突起伸長 / ガンの増殖・転移 / カドヘリン / インテグリン / 細胞外マトリックス / 骨格筋分化 / 骨粗鬆症 / 糖鎖生物学 / ガンの転移 / エンドサイトーシス / 乳ガン / β-カテニン / コンドロチン硫酸 |
Outline of Final Research Achievements |
Chondroitin sulfate proteoglycans have been implicated as regulators of a variety of biological events, including cell-cell and cell-matrix adhesion, cell proliferation, morphogenesis, and neurite outgrowth. Many of the physiological roles of chondroitin sulfate proteoglycans are attributed to the chondroitin sulfate side chains. In this study, we found that a fucosylayed chondroitin sulfate from A. japonicus promotes neurite outgrowth as well as chondroitin sulfate-E through BDNF signaling and that chondroitin sulfate-D-mediated neurite outgrowth is exerted via neuronal cell surface integrin αVβ3. In addition, we showed that binding of chondroitin sulfate-E to N-cadherin triggers endocytosis-dependent activation of the N-cadherin/β-catenin pathway to enhance the metastatic properties of a basal-like breast cancer cell line BT-549.
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Academic Significance and Societal Importance of the Research Achievements |
本研究から、コンドロイチン硫酸鎖を認識する新たな受容体が複数同定され、神経分化・再生やがん細胞の増殖・浸潤過程でもコンドロイチン硫酸鎖がシグナル分子として機能することが明らかとなった。本研究の成果は、コンドロイチン硫酸鎖の発現や構造をコントロールすることによって、神経分化・再生やがん細胞の増殖・浸潤が制御可能であることを示し、学術的にも意義深い。また、従来の作用点とは全く異なる革新的な治療薬の開発が可能になると思われる。
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Report
(4 results)
Research Products
(87 results)
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[Journal Article] Chondroitin sulfate N-acetylgalactosaminyltransferase-2 deletion alleviates lipoprotein retention in early atherosclerosis and attenuates aortic smooth muscle cell migration.2019
Author(s)
Adhikara IM, Yagi K, Mayasari DS, Ikeda K, Kitagawa H, Miyata O, Igarashi M, Hatakeyama K, Asada Y, Hirata KI, Emoto N
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Journal Title
Biochem Biophys Res Commun
Volume: 509
Issue: 1
Pages: 89-95
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Synthesis of chondroitin sulfate CC and DD tetrasaccharides and interactions with 2H6 and LY111.2018
Author(s)
Matsushita, K., Nakata, T., Takeda-Okuda, N., Nadanaka, S., Kitagawa, H., and Tamura, J.
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Journal Title
Bioorg. Med. Chem.
Volume: 26
Issue: 5
Pages: 1016-1016
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] FLUORESCENCE QUENCHING INDUCED BY SEQUENTIAL ADDITION-AROMATIZATION OF A BODIPY-CONTAINING DIENYLIMINE WITH THIOLS2017
Author(s)
Takeda, N., Ueda M., Mori, N., Miyoshi, T., Shimoda, M., Uno, Y., Kitagawa, H., Emoto, N., Mukai, T., and Miyata, O.
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Journal Title
HETEROCYCLES
Volume: 94(4)
Issue: 4
Pages: 750-762
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Chondroitin Sulfate Is Required for Onset and Offset of Critical Period Plasticity in Visual Cortex2017
Author(s)
Hou X, Yoshioka N, Tsukano H, Sakai A, Miyata S, Watanabe Y, Yanagawa Y, Sakimura K, Takeuchi K, Kitagawa H, Hensch TK, Shibuki K, Igarashi M, Sugiyama S
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Journal Title
Scientific Reports
Volume: 7
Issue: 1
Pages: 12646-12646
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Antibody recognising 4-sulphated chondroitin sulphate proteoglycans restores memory in tauopathy-induced neurodegeneration.2017
Author(s)
Yang, S., Hilton, S., Alves, J. N., Saksida, L. M., Bussey, T. M., Matthews, R. T., Kitagawa, H., Spillantini, M. G., Kwok, J. C. F., and Fawcett, J. W.
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Journal Title
Neurobiol. Aging
Volume: 59
Pages: 197-209
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Chondroitin sulfate β-1,4-N-acetylgalactosaminyltransferase-1 (ChGn-1) polymorphism; association with progression of multiple sclerosis.2016
Author(s)
Saigoh, K., Yoshimura, S., Izumikawa, T., Miyata, S., Tabara, Y., Matsushita, T., Miki, T., Miyamoto, K., Hirano, M., Kitagawa, H., Kita, J., and Kusunoki, S.
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Journal Title
Neurosci. Res.
Volume: 印刷中
Pages: 55-59
DOI
Related Report
Peer Reviewed
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[Journal Article] Chondroitin 4-O-sulfotransferase is indispensable for sulfation of chondroitin and plays an important role in maintaining normal life span and oxidative stress responses in nematodes.2016
Author(s)
Izumikawa, T., Dejima, K., Watamoto, Y., Nomura, K. H., Kanai, N., Rikitake, M., Tou, M., Murata, D., Yanagita, E., Kano, A., Mitani, S., Nomura, K., and Kitagawa, H.
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Journal Title
J. Biol. Chem.
Volume: 291
Issue: 44
Pages: 23294-23304
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Presentation] A novel glycotechnology to produce human lysosomal enzymes carrying synthetic N-glycans with terminal mannose 6-phosphate residues and application to enzyme placement therapy for lysosomal diseases.2018
Author(s)
Itoh, K., Nishioka, S., Kobayashi, I., Matsuzaki, Y., Iino, K., Nadanaka, S., Kasashima-Sumitani, M., Hidaka, T., Tsuji, D., Sezutsu, H., Kitagawa, H., Yamamoto, K.
Organizer
14th ANNUAL WORLD Symposium
Related Report
Int'l Joint Research
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[Presentation] Change in EXTL2, A Novel Factor Related to Vascular Calcification, in Hemodialysis Patients.2017
Author(s)
Shunsuke Goto, Hideki Fujii, Satomi Nadanaka, kentaro Watanabe, Shuhei Watanabe, Keiji Kono, Shohei Nakanishi, John-Il Kim, Hiroshi Kitagawa, Shinichi Nishi
Organizer
KIDNEY WEEK 2017
Related Report
Int'l Joint Research
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