2007 Fiscal Year Final Research Report Summary
Studies on the formation mechanism and functions of the covalently bound complex of hyaluronan with SHAP, the functional molecular entity of hyaluronan
Project/Area Number |
17370041
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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 |
Structural biochemistry
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Research Institution | Aichi Medical University |
Principal Investigator |
KIMATA Koji Aichi Medical University, Emeritus professor (10022641)
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Co-Investigator(Kenkyū-buntansha) |
LISHENG Zhuo Aichi Medical University, Institute of Molecular Science of Medicine, Research Associate (00399031)
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Project Period (FY) |
2005 – 2007
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Keywords | hyaluronan / SHAP / inflammation / inter-α-trypsin inhibitor / complex-forming enzyme factor / hepatitis / TSG-6 / compliment |
Research Abstract |
The covalently bound complex formed from inter-α-trypsin inhibitor (ITI) and hyaluronan (HA) by transesterification reaction, the SHAP (ITI heavy chain)-HA complex was investigated with regard to its physiological functions and serum enz; yme factors involved in the reaction. The candidate protein obtained from one of the library of serum fractions by the beforehand establisehd purification methods using a series of affinity columns was identified FHR-1 (factor H-related protein-1). However, the medium fraction of FHR-1 cDNA-transfected hepatocarcinoma HLF cells did not show any of the activity. Meanwhile, we found that the medium of the transfectants with cDNA of TSG-6 (TNFα-stimulated gene 6 product) had the dramatically increased activity that was yet retained after removal of TSG-6 by passing through the antibody affinity column, suggesting that the enzyme factors could not be TSG-6 itself and be induced with TSG-6 in the cells. Thus, we are now in the processes to the purification
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and identification of the factors. We previously developed the bikunin (ITI short chain)-knockout mouse system in order to investigate in vivo functions of the SHAP-HA complex where the complex was not formed. We found that the knockout mouse was resistant to the induction of acute hepatitis by the administration of D-galactosamine/E.coli lipopolysaccharide (LPS) in which the CD44-HA interaction-dependent attachment of neutrophils to live capillary sinusoidal cell surfaces was involved in response to the LPS stimuli. We then found using culthred leukocytes that the SHAP-HA complex activates the CD44-HA interaction-dependent cell adhesion more than 100 times, which is a decisive evidence for the involvement of the SHAP-HA complex in inflammatory cell response. We also found the good relationship between the SHAP-HA complex levels and the disease progression in the serum samples from patients of liver diseases, articular cartilage injury, gestoses, ovarian cancer etc, suggesting functional significances of the SHAP-HA complex in those diseases and the high reliability of the complex as a disease marker. Less
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Research Products
(140 results)
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[Journal Article] Characterization of a motif for specific binding to hyaluronan in chicken SPACR.2008
Author(s)
Zhao J, Yoneda M, Takeyama M, Miyaishi O, Inoue Y, Kataoka T, Ohno-Jinno A, Isogai Z, Kimata K, Iwaki M, Zako M
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Journal Title
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Versican and Fibrillin-1 Form a Major Hyaluronan-Binding Complex in the Ciliary Body2008
Author(s)
Ohno-Jinno A, Isogai Z, Yoneda M, Kasai K, Miyaishi O, Inoue Y, Kataoka T, Zhao JS, Li H, Takeyama M, Keene DR, Sakai LY, Kimata K, Iwaki M, Zako M
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Journal Title
Invest Ophthalmol Vis Sci (In press)
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Significance of Tumor-Associated Stroma in Promotion of Intratumoral Lymphangiogenesis.Pivotal Role of a Hyaluronan-Rich Tumor Microenvironment2008
Author(s)
Koyama H, Kobayashi N, Harada M, Takeoka M, Kawai Y, Sano K, Fujimori M, Amano J, Ohhashi T, Kannagi R, Kimata K, Taniguchi S, Itano N
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Journal Title
Am J Pathol 172(1)
Pages: 179-193
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Characterization of a motif for specific binding to hyaluronan in chicken SPACR2008
Author(s)
Zhao J, Yoneda M, Takeyama M, Miyaishi O, Inoue Y, Kataoka T, Ohno-Jinno A, Isogai Z, Kimata K, Iwaki M, Zako M.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Versican and Fibrillin-1 Form a Major Hyaluronan-Binding C omplex in the Ciliary Body.2008
Author(s)
Ohno-Jinno A, Isogai Z, Yoneda M, Kasai K, Miyaishi O, Inoue Y, Kataoka T, Zhao JS, Li H, Takeyama M, Keene DR, Sakai LY, Kimata K, Iwaki M, Zako M.
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Journal Title
Invest Ophthalmol Vis Sci. (in press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Significance of Tumor-Associated Stroma in Promotion of Intratumoral Lymphangiogenesis. Pivotal Role of a Hyaluronan-Rich Tumor Micro-environment.2008
Author(s)
Koyama H, Kobayashi N, Harada M, Takeoka M, Kawai Y, Sano K, Fujimor M, Amano J, Ohhashi T, Kannagi R, Kimata K, Taniguchi S, Itano N.
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Journal Title
Am J Pathol. 172(1)
Pages: 179-193
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Hyperproduction of hyaluronan in neu-induced mammary tumor accelerates angiogenesis through stromal cell recrutitment:possible involvement of versican/PG-M2007
Author(s)
Koyama H, Hibi T, Isogai Z, Yoneda M, Fujimori M, Amano J, Kawakubo M, Kannagi R, Kimata K, Taniguchi S, Itano N
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Journal Title
Am J Pathol 170
Pages: 1086-99
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Hyperproduction of hyaluro-nan in neu-induced mammary tumor accelerates angiogenesis through stromal cell recrutitment : possible involvement of versican/PG-M.2007
Author(s)
Koyama H, Hibi T, Isogai Z, Yoneda M, Fujimori M, Amano J, Kawakubo M, Kannagi R, Kimata K, Taniguchi S, Itano N.
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Journal Title
Am J Pathol. 170
Pages: 1086-99
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] SHAP potentiates the CD44-mediated leukocyte adhesion to the hyaluronan substratum2006
Author(s)
Zhuo, L., Kanamori, A., Kannagi, R., Itano, N., Wu, J., Hamaguchi, M., Ishiguro, N., Kimata, K
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Journal Title
J Biol Chem. 281(29)
Pages: 20303-20314
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Molecular cloning and characterization of chick SPACRCAN2006
Author(s)
Inoue, Y., Yoneda, M., Zhao, J., Miyaishi, O., Ohno-Jinno, A., Kataoka, T., Isogai, Z., Kimata, K., Iwaki, M., Zako, M.
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Journal Title
J Biol Chem 281
Pages: 10381-10388
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] The SHAP-hyaluronan complex in serum from patients with chronic liver diseases caused by hepatitis virus infection2006
Author(s)
Shen L, Zhuo L, Okumura A, Ishikawa T, Miyachi M, Owa Y, Ishizawa T, Sugiura N, Nagata Y, Nonami T, Kakumu S, Kimata K
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Journal Title
Hepatol Res 1376
Pages: 1-9
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] SHAP potentiates the CD44-mediated leukocyte adhesion to the hyaluronan substratum.2006
Author(s)
Zhuo, L., Kanamori, A., Kannagi, R., Itano, N., Wu, J., Hamaguchi, M., Ishiguro, N., Kimata, K.
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Journal Title
J Biol Chem. 281(29)
Pages: 20303-20314
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Molecular cloning and characterization of chick SPACRCAN.2006
Author(s)
Inoue, Y., Yoneda, M., Zhao, J., Miyaishi, O., Ohno-Jinno, A., Kataoka, T., Isogai, Z., Kimata, K., Iwaki, M., Zako, M.
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Journal Title
J Biol Chem. 281
Pages: 10381-10388
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The SHAP-hyalu-ronan complex in serum from patients with chronic liver diseases caused by hepatitis virus infection.2006
Author(s)
Shen L, Zhuo L, Okumura A, Ishikawa T, Miyachi M, Owa Y, Ishizawa T, Sugiura N, Nagata Y, Nonami T, Kakumu S, Kimata K.
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Journal Title
Hepatol Res. 28, 1376
Pages: 1-9
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Expression of a chondroitin sulfate proteoglycan,versican (PG-M),during development of rat cornea2005
Author(s)
Koga T, Inatani M, Hirata A, Inomata Y, Zako M, Kimata K, Oohira A, Gotoh T, Mori M, Tanihara H
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Journal Title
Curr Eye Res 30
Pages: 455-463
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Identification and characterization of photomedins:novel olfactomedin-domain-containing proteins with chondroitin sulphate-E-binding activity2005
Author(s)
Furutani Y, Manabe R, Tsutsui K, Yamada T, Sugimoto N, Fukuda S, Kawai J, Sugiura N, Kimata K, Hayashizaki Y, Sekiguchi K
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Journal Title
Biochem J 389
Pages: 675-684
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Expression of a chondroitin sulfate proteo-glycan, versican(PG-M), during development of rat cornea2005
Author(s)
Koga T, Inatani M, Hirata A, Inomata Y, Zako M, Kimata K Oohira A, Gotoh T, Mori M, Tanihara H.
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Journal Title
Curr Eye Res. 30
Pages: 455-463
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Identification and characterization of photornedins : novel olfactomedin-domain-contain-ing proteins with chondroitin sulphate-E-binding activity.2005
Author(s)
Furutani Y, Manabe R, Tsutsui K, Yamada T, Sugimoto N, Fukuda S, Kawai J, Sugiura N, Kimata K, Hayashizaki Y, Sekiguchi K.
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Journal Title
Biochem J. 389
Pages: 675-684
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A mechanism for 4-methylumbelliferone-mediated inhibition of hyaluronan biosynthesis.2005
Author(s)
Itano, N., Kakizaki, I., Mita, S., Endo, M., Kimata. K.
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Journal Title
In Hyaluronan Structure, Metabolism, Biological Activities, Therapeutic Applications(Balazs E. A., and Hascall, V. C., eds), Volume Matrix Biology Institute, New Jersey, U.S.A.
Pages: 147-53
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Role of serum-derived hyaluronan-associated protein in the construction of cumulus matrix and oocyte maturation.2005
Author(s)
Zhuo, L, Salustri, A, Atsumi, F, Kawano, M, Wu, J, Shen, L, Ogura, A, Yasue, H, Hascall, VC, Kimata. K.
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Journal Title
In Hyaluronan Structure, Metabolism, Biological Activities, Therapeutic Applications(Balazs, E. A., and Hascall, V. C., eds), Volume II Matrix Biology Institute, New Jersey, U.S.A.
Pages: 731-5
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Hyaluronan-Iinked inter-alpha-trypsin inhibitor heavy chain(SHAP),interleukin 8,MMP-3 and hyaluronan in human synovial fluid and serum in osteoarthritis,joint injury and inflammation2007
Author(s)
Lohmander L, Zhu L, Zhuo L, X-Y RS, Ma K, Blake S, Kimata K
Organizer
53rd Annual Meeting of the Orthopaedic Research Society(ORS)
Place of Presentation
San Diego,CA,USA
Year and Date
20070211-14
Description
「研究成果報告書概要(和文)」より
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[Presentation] Hyaluro. nan-Iinked inter-alpha-trypsin inhibitor heavy chain(SHAP), interleukin 8, MMP-3 and hyaluronan in human synovial fluid and serum in osteo-arthritis2007
Author(s)
Lohmander L, Zhu L, Zhuo L, X-Y RS, Ma K, Blake S, Kimata K.
Organizer
53rd Annual Meeting of the Orthopaedic joint injury and inflammation Research Society(ORS)
Place of Presentation
San Diego, CA, USA
Year and Date
20070211-14
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Hyaluronan-iinked inter-alpha-trypsin inhibitor heavy chain (SHAP),interleukin 8,and hyaluronan in human synovial fluid and serum in osteoarthritis,joint injury and inflammation2006
Author(s)
Lohmander L, Zhu L, Zhuo L, X-Y RS, Ma K, Blake S, Kimata K
Organizer
The Osteoarthritis research society international(OARSI) world congress on osteoarthritis
Place of Presentation
Prague,Czech Republic
Year and Date
20061207-10
Description
「研究成果報告書概要(和文)」より
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[Presentation] Hyalu-ronan-iinked inter-alpha-trypsin inhibitor heavy chain(SHAP), inter leukin 8, and hyaluronan in human synovial fluid and serum in osteo-arthritis, joint injury and inflammation.2006
Author(s)
Lohmander L, Zhu L, Zhuo L, X-Y RS, Ma K, Blake S, Kimata K.
Organizer
International(OARSI) world congress on osteoarthritis
Place of Presentation
Prague, Czech Republic
Year and Date
20061207-10
Description
「研究成果報告書概要(欧文)」より
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[Presentation] VERSICAN/PG-M is essential for mic cardiovascular and dermal development.2006
Author(s)
Hatano S, Kimata K, Hiraiwa N, Kusakabe M, Adachi E, Isogai Z, Shinomura T, Watanabe H.
Organizer
20th IUBMB international congress of biochmistry and molecular biology and 11th FAOBMB congress in conjunction with 79th annual meeting of the Japanese biochemical society and 29th annual meeting of the molecular iology society of Japan
Place of Presentation
Kyoto Kyoto International Conference Center
Year and Date
20060618-23
Description
「研究成果報告書概要(欧文)」より
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[Presentation] 軟骨分化における糖鎖合成酵素の発現2005
Author(s)
坂井 顕一郎, 木全 弘治, 渥美 ふき子, 成松 久, 四宮 謙一, 渡辺 秀人
Organizer
第18回日本軟骨代謝学会
Place of Presentation
大阪
Year and Date
2005-03-18
Description
「研究成果報告書概要(和文)」より
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[Book] Hyaluronan Structure, Metabolism, Biological Activities, Therapeutic Applications2005
Author(s)
Itano, N., Kakizaki, I., Mita, S., Endo, M., Kima K
Total Pages
7
Publisher
Matrix Biology Institute
Description
「研究成果報告書概要(和文)」より
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[Book] Hyaluronan Structure, Metabolism, Biological Activities, Therapeutic Applications2005
Author(s)
Zhuo, L., Salustri, A., Atsumi, F., Kawano, M., Wu, J., Shen, L., Ogura, A., Yasue, H., Hascall, V.C., Kimata, K
Total Pages
5
Publisher
Matrix Biology Institute
Description
「研究成果報告書概要(和文)」より
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