The role of glycosaminoglycan in neuronal injuries

• Project/Area Number: 18390099
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Nagoya University
• Principal Investigator: KADOMATSU Kenji Nagoya University, Graduate School of Medicine, Professor (80204519)
• Co-Investigator(Kenkyū-buntansha): MATSUYAMA Yukihiro Nagoya University, Graduate School of Medicine, Associate Professor (20312316) ; KISHIDA Satoshi Nagoya University, Graduate School of Medicine, Assistant Professor (20402563)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥16,460,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥1,560,000); Fiscal Year 2007: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000); Fiscal Year 2006: ¥9,700,000 (Direct Cost: ¥9,700,000)
• Keywords: Proteoglycan / Keratan sulfate / Chondroitn sulfate / Glycosaminoglycan / Midkine / 神経損傷 / 神経再生

Research Abstract

Non-permissive cues, such as chondroitin sulfate proteoglycans (CSPGs) and semaphorin, inhibit neuronal axon regeneration together with glial scar after neuronal injuries. In this study we focused on chondroitin sulfate (CS) and keratan sulfate (KS) with regards to their inhibitory activity against axonal regeneration. We found that N-acetylglucosamine6-O-sulfotransferase (GlcNAc6ST) -1in involved in KS biosynthesis in the central nervous system. Upon cortical stab wound, CS and KS expression was induced at the injury site in wild-type mice, while CS expression was only induced but KS was undetectable in GIcNAc6ST-deficient mice. GIcNAc6ST-deficient mice showed more axonal regeneration than wild-type mice did. To further investigate the role of KS in neuronal injuries, we made contusion injuries to the spinal cord. GIcNAc6ST-deficient mice exhibited reduced glial scar formation, enhanced axonal regeneration and consequently better recovery of motor function as compared with wild-type mice. Our data suggest that KS plays an indispensable role in inhibition of neuronal axon regeneration after injuries.

Research Products

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  • Author(s): Mu, P., Nagahara, S., Makita, N., Tarumi, Y., Kadomatsu, K., Takei, Y.
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  • Description: 「研究成果報告書概要(和文)」より
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• [Journal Article] Transforming growth factor-β_1 upregulates keratan sulfate and chondroitin sulfate biosynthesis in microglias after brain injury. (2009)
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• [Journal Article] Midkine prevents ventricular remodeling and improves long-term survival after myocardial infarction. (2009)
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  • Journal Title: Am. J. Physiol. Heart Circ. Physiol. 296 Pages: 462-469
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• [Journal Article] Systemic delivery of siRNA specific to tumor mediated by atelocollagen Combined therapy using siRNA targeting Bcl-xL and cisplatin against prostate cancer (2009)
  • Author(s): Mu, P., Nagahara, S., Makita, N., Tarumi, Y, Kadomatsu, K., Takei, Y.
  • Journal Title: Int. J. Cancer (In press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Transforming growth factor-β upregulates keratan sulfate and chondroitinsulfate biosynthesis in microglias after brain injury. (2009)
  • Author(s): Yin, J., Sakamoto, K., Zhang, H., Ito, Z., Imagama, S., Kishida, S., Natori, T., Sawada, M., Matsuyama, Y., Kadomatsu, K.
  • Journal Title: Brain Res. (In press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Midkine prevents ventricular remodeling and improves long-term survival after myocardial infarction. (2009)
  • Author(s): Takenaka, H., Horiba, M., Ishiguro, H., Sumida, A., Hojo, M., Usui, A., Akita, T, Sakuma, S., Ueda, Y, Kodama, I., Kadomatsu, K.
  • Journal Title: Am. J. Physiol. Heart Circ. Physio. l 296
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Transforming growth factor-β_1 upregulates keratan sulfate and chondroitin sulfate biosynthesis in microglias after brain injury (2009)
  • Author(s): Yin, J., Sakamoto, K., Zhang, H., Ito, Z., Imagama, S., Kishida, S., Natori, T., Sawada, M., Matsuyama, Y., Kadomatsu, K
  • Journal Title: Brain Res. (In press)
  • Peer Reviewed
• [Journal Article] Midkine prevents ventricular remodeling and improves long-term survival after myocardial infarction (2009)
  • Author(s): Takenaka, H., Horiba, M., Ishiguro, H., Sumida, A., Hojo, M., Usui, A., Akita, T., Sakuma, S., Ueda, Y., Kodama, I., Kadomatsu, K.
  • Journal Title: Am. J. Physiol. Heart Circ. Physiol 296
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• [Journal Article] Expression and roles of a xenopus head-forming gene homologue in human cancer cell lines. (2008)
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  • NAID: 110007018287
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Removal of blood group A/B antigen in organs by ex vivo and in vivo administration of ando-p-galactosidase (ABase) for ABO incompatible transplantation. (2008)
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  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Plasma midkine levelils a prognostic factor for human neurobiastoma (2008)
  • Author(s): Ikematsu, S., Nakagawara, A., Nakamura, Y., Ohira, M., Shinjo, M., Satoshi, Kishida, S., Kadomatsu, K.
  • Journal Title: Cancer Sci. 99 Pages: 2070-2074
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Basal and stimulated lactate fluxes in primary cultures of astrocytes are differentially controlled by distinct proteins. (2008)
  • Author(s): Maekawa, F., Minehira, K., Kadomatsu, K., Pellerin, L.
  • Journal Title: J. Neurochem. 107 Pages: 789-798
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Midkine and its clinical significance in endometrial carcinoma. (2008)
  • Author(s): Tanabe, K, Matsumoto, M., Ikematsu, S., Nagase, S., Hatakeyama, A., Takano, T., Niikura, H., Ito, K., Kadomatsu, K., Hayashi, S., Yaegashi, N.
  • Journal Title: Cancer Sci. 99 Pages: 1125-1130
  • NAID: 10024007074
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] In vivo silencing of a molecular target by short interfering RNA electroporation : Tumor vascularization correlates to delivery efficiency. (2008)
  • Author(s): Takei, Y, Nemoto, T., Mu, P., Fujishima, T., Ishimoto, T., Hayakawa, Y, Yuzawa, Y, Matsuo, S., Muramatsu, T., Kadomatsu, K.
  • Journal Title: Mol. Cancer Ther. 7 Pages: 211-221
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Downregulation of monocyte chemoattractant protein-1 involving short interfering RNA attenuates Hapten-induced contact hypersensitivity (2008)
  • Author(s): Ishimoto, T., Takei, Y. Yuzawa, Y, Hanai, K., Nagahara, S., Tarumi, Y, Matsuo, S., Kadomatsu, K.
  • Journal Title: Mol. Ther. 16 Pages: 387-395
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Midkine is expressed by infiltrating macrophages in in-stent restenosis in hypercholesterolemic rabbits (2008)
  • Author(s): Narita, H., Chen, S., Komori, K., Kadomatsu, K.
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• [Journal Article] 波及・深化する糖鎖研究 糖鎖の持つ多彩な機能の解析と疾患研究に与えるインパクト (2007)
  • Author(s): 門松健治
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• [Journal Article] Ginger ingredients reduce viability of gastric cancer cells via distinct mechanisms. (2007)
  • Author(s): Ishiguro, K., Ando, T., Maeda, O., Ohmiya, N., Niwa, Y., Kadomatsu, K, Goto H.
  • Journal Title: Biochem. Biophys. Res. Commun. 362 Pages: 218-223
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Relation between human decay-accelerating factor (hDAF) expression in pig cells and inhibition of human serum anti-pig cytotoxicity : value of highly expressed hDAF for Xenotransplantation. (2007)
  • Author(s): Liu, D., Kobayashi, T., Onishi, A., Furusawa, T., Iwamoto, M., Suzuki, S., Miwa, Y, Nagasaka, T., Maruyama, S., Kadomatsu, K., Uchida, K., Nakao, A.
  • Journal Title: Xenotransplantation 14 Pages: 67-73
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Midkine as a novel target for antibody therapy in osteosarcoma. (2007)
  • Author(s): Maehara, H., Kaname, T., Yanagi, K., Hanzawa, H., Owan, I., Kinjou, T., Kadomatsu, K., Ikematsu, S., Iwamasa, T., Kanaya, F., Naritomi, K.
  • Journal Title: Biochem Biophys Res Commun. 358 Pages: 757-762
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Increased midkine gene expression in childhood B-precursor acute lymphoblastic leukemia. (2007)
  • Author(s): Hidaka, H., Hiroshi Yagasaki, H. Takahashi, Y., Hama, A., Nishio, N., Makito Tanaka, M, Yoshida, N., Villalobos, I. B., Wang, Y, Xu. Y. Y., Horibe, K., Chen, S., Kadomatsu, K., Kojima, S.
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  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Midkine and LDL receptor-related protein 1 contribute to the anchorage-independent cell growth of cancer cells. (2007)
  • Author(s): Chen, S., Bu, G., Takei, Y., Sakamoto, K., Ikematsu, S., Muramatsu, T., Kadomatsu, K.
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• [Journal Article] Midkine is involved in tubulo-interstitial inflammation associated with diabetic nephropathy. (2007)
  • Author(s): Kosugi, T, Yuzawa, Y, Sato, W., Kato, N., Arata-Kawai, H., Matsuo, S., Kadomatsu. K.
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• [Journal Article] Midkine plays a protective role against cardiac ischemia/reperfusion in jury through a reduction of apoptotic reaction. (2006)
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• [Journal Article] Growth factor midkine is involved in the pathogenesis of diabetic nephropathy. (2006)
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• [Journal Article] N-acetylglucosamine 6-O-sulfotransferase-1 is required for brain keratan sulfate biosynthesis and glial scar formation after brain injury. (2006)
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• [Journal Article] Paeonol attenuates TNBS-induced colitis by inhibiting NF-kappaB and STAT1 transactivation (2006)
  • Author(s): Ishiguro, K., Ando, T, Maeda, O., Hasegawa, M., Kadomatsu, K., Ohmiya, N., Niwa, Y., Xavier, R., Goto, H.
  • Journal Title: Toxicol. Appl. Pharmacol. 217 Pages: 35-42
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Loss of core fucosylation of low-density lipoprotein receptor-related protein-1 impairs its function leading to the upregulation of serum levels of insulin-like growth factor-binding protein 3 in fut8-/- mice. (2006)
  • Author(s): Lee, S. H., Takahashi, M., Honke, K., Miyoshi, E., Osumi, D., Sakiyama, H., Ekuni, A., Wang, X., Inoue, S., Gu, J., Kadomatsu, K., Taniguchi, N.
  • Journal Title: J. Biochem. 139 Pages: 391-398
  • NAID: 10018846392
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Midkine plays a protective role against cardiac ischemia/reperfusion injury through a reduction of apoptotic reaction. (2006)
  • Author(s): Horiba, M., Kadomatsu, K., Yasui, K., Lee, J., Takenaka, H., Sumida, A., Kamiya, K., Chen, S., Sakuma, S., Muramatsu, T., Kodama, I.
  • Journal Title: Circulation 114 Pages: 1713-1720
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Controlled release of siRNA as to midkine attenuates intimal hyperplasia in vein grafts. (2006)
  • Author(s): Banno, H., Takei, Y, Muramatsu, T, Komori, K., Kadomatsu, K.
  • Journal Title: J. Vas. Surg. 44 Pages: 633-641
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Combinational antitumor effect of siRNA as to midkine and paclitaxel on growth of human prostate cancer xenografts (2006)
  • Author(s): Takei, Y., Kadomatsu, K., Goto, T., Muramatsu, T.
  • Journal Title: Cancer 107 Pages: 864-873
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Growth factor midkine is involved in the pathogenesis of diabetic Nephropathy. (2006)
  • Author(s): Kosugi, X, Yuzawa, Y, Sato, W., Kawai, H., Matsuo, S., Takei, Y., Muramatsu, T., Kadomatsu, K.
  • Journal Title: Am. J. Pathol. 168 Pages: 9-19
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] W-acetylglucosamine 6-O-sulfotransferase-1 is required for brain keratan sulfate biosynthesis and glial scar formation after brain injury. (2006)
  • Author(s): Zhang, H., Muramatsu, T., Murase, A., Yuasa, S., Uchimura, K., Kadomatsu, K.
  • Journal Title: Glycobiology 16 Pages: 702-710
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] keratan sulfate and glial scar formation. (2006)
  • Author(s): Zhang, H., Uchimura, K., Kadomatsu, K.
  • Journal Title: Ann. NY Acad, Sci. 1086 Pages: 81-90
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] N-acetylglucosamine 6-O-sulfotransferase-1 is required for brain keratan sulfate biosynthesis and glial scar formation after brain injury. (2006)
  • Author(s): Zhang, H.
  • Journal Title: Glycobiology 16 Pages: 702-710
• [Journal Article] Brain keratan sulfate and glial scar formation. (2006)
  • Author(s): Zhang, H.
  • Journal Title: Ann. NY Acad. Sci. 1086 Pages: 81-90
• [Journal Article] Growth factor midkine is involved in the pathogenesis of diabetic nephropathy. (2006)
  • Author(s): Kosugi, T.
  • Journal Title: Am. J. Pathol. 168 Pages: 9-19
• [Journal Article] Combinational antitumor effect of siRNA as to midkine and paclitaxel on growth of human prostate cancer xenografts. (2006)
  • Author(s): Takei, Y.
  • Journal Title: Cancer 107 Pages: 864-873
• [Journal Article] Controlled release of siRNA as to midkine attenuates intimal hyperplasia in vein grafts. (2006)
  • Author(s): Banno, H.
  • Journal Title: J. Vas. Surg. 44 Pages: 633-641
• [Journal Article] Midkine plays a protective role against cardiac ischemia/reperfusion injury through a reduction of apoptotic reaction. (2006)
  • Author(s): Horiba, M.
  • Journal Title: Circulation 114 Pages: 1713-1720
• [Presentation] 神経軸索再生とケラタン硫酸 (2008)
  • Author(s): 門松健治
  • Organizer: 第31回神経科学会大会
  • Place of Presentation: 東京
  • Year and Date: 2008-07-10
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 神経軸索の再生とケラタン硫酸 (2008)
  • Author(s): 門松健治
  • Organizer: 第23回神経組織の成長・再生・移植研究会学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2008-05-17
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Neuronal axon regeneration and keratan sulfate. (2008)
  • Author(s): Kadomatsu, K.
  • Organizer: 23^<rd> Meeting of Neuroscience
  • Place of Presentation: Chiba
  • Year and Date: 2008-05-17
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 脊髄損傷は治せるか? (2008)
  • Author(s): 門松健治
  • Organizer: 第18回名古屋大学高等研究院セミナー
  • Place of Presentation: 名古屋
  • Year and Date: 2008-01-22
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Can we cure spinal cord injury? (2008)
  • Author(s): Kadomatsu, K.
  • Organizer: 18^<th> Seminar of Institute for Advanced Research Nagoya University
  • Place of Presentation: Nagoya
  • Year and Date: 2008-01-22
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Role of glycosaminoglycan in axonal regeneration (2008)
  • Author(s): 門松健治
  • Organizer: 第81回日本生化学会大会
  • Place of Presentation: 神戸
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Role of glycosaminoglycan in axonal regeneration. (2008)
  • Author(s): Kadomatsu, K.
  • Organizer: 81^<st> Meeting of Japanese Biochemistry Society
  • Place of Presentation: Kobe
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Neuronal axon regeneration and keratan sulfate. (2008)
  • Author(s): Kadomatsu, K.
  • Organizer: 31^<s1> Meeting of Neuroscience
  • Place of Presentation: Tokyo
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 神経損傷とケラタン硫酸 (2007)
  • Author(s): 門松健治
  • Organizer: 第5回糖鎖科学コンソーシアシンポジウム
  • Place of Presentation: 東京
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Neuronal Injury and keratan sulfate. (2007)
  • Author(s): Kadomatsu, K.
  • Organizer: 5^<th> Consotium of Glycobiology.
  • Place of Presentation: Tokyo
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] N-acetylglucosamine 6-O-sulfotransferase-1 is required for brain keratan sulfate biosynthesis and glial scar formation after brain injury. (2006)
  • Author(s): Kadomatsu, K. Zhang, H., Uchimura, K., Muramatsu, T.
  • Organizer: 5^<th> International Symposium on Glycosyltransferases. GlycoT
  • Place of Presentation: Tukuba
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] N-acetylglucosamine 6-0-sulfotransferase-1 is required for brain keratan sulfate biosynthesis and glial scar formation after brain injury. (2006)
  • Author(s): Kadomatsu, K. Zhang, H., Uchimura, K., Muramatsu, T.
  • Organizer: 5^<th> International Symposium on Glycosyltransferases. GlycoT.
  • Place of Presentation: Tsukuba
  • Description: 「研究成果報告書概要(欧文)」より
• [Patent(Industrial Property Rights)] 神経傷害に基づく機能不全の改善剤およびRhoキナーゼ活性化抑制剤 (2007)
  • Inventor(s): 門松健治, 松山幸弘, 田中昭臣, 竹下佐和子
  • Industrial Property Rights Holder: 名古屋大学, (株)生化学工業
  • Industrial Property Number: 2007-173487
  • Filing Date: 2007-06-29
  • Description: 「研究成果報告書概要(和文)」より