Growth factor and extracellular matrix in neural reconstruction

• Project/Area Number: 20390092
• 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 名古屋大学, 大学院・医学系研究科, 教授 (80204519)
• Co-Investigator(Kenkyū-buntansha): TAKEI Yoshifumi 名古屋大学, 医学系研究科, 准教授 (70362233) ; IMAGAMA Shirou 名古屋大学, 医学部附属病院, 助教 (40467288) ; KISHIDA Satoshi 名古屋大学, 医学系研究科, 助教 (20402563) ; 松山 幸弘 名古屋大学, 医学系研究科, 准教授 (20312316)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥19,760,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥4,560,000); Fiscal Year 2010: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2009: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2008: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
• Keywords: ケラタン硫酸 / コンドロイチン硫酸 / プロテオグリカン / 軸索再生・分枝 / 神経可塑性 / 神経損傷 / 成長因子 / 脊髄損傷 / グリコサミノグリカン / ミッドカイン

Research Abstract

Axonal regeneration/sprouting hardly occur after neuronal injuries, mainly due to induction of inhibitory factors. Chondroitin sulfate is one of most well-known inhibitory factors. We found that keratan sulfate inhibits axonal regeneration/sprouting, and its inhibitory activity is as strong as that of chondroitin sulfate. For the inhibition, all the components of proteoglycans(i. e., keratan sulfate, chondroitin sulfate, core protein) are required. Our data suggest that an appropriate presentation of keratan sulfate and chondroitin sulfate by the core protein is important, and these sugar chains may be read by receptor(s) on neurons.

Research Products

• [Journal Article] Midkine Gene Transfer after Myocardial Infarction in Rats Prevents Remodeling and Ameliorates Cardiac Dysfunction (2010)
  • Author(s): Sumida A, Horiba M, Ishiguro H, Takenaka H, Ueda N, Ooboshi H, Opthof T, Kadomatsu K, Kodama I
  • Journal Title: Cardiovasc Res Volume: 86 Pages: 113-121
  • Peer Reviewed
• [Journal Article] N-acetylglucosamine 6-O-sulfotransferase-1-deficient Mice Show Better Functional Recovery after Spinal Cord Injury (2010)
  • Author(s): Ito, Z., Sakamoto, K., Imagama, S., Matsuyama, Y., Zhang, H., Hirano, K., Ando, K., Yamashita, T., Ishiguro, N., Kadomatsu, K
  • Journal Title: J. Neurosci Volume: 3 Pages: 5937-5947
  • NAID: 120005946850
  • Peer Reviewed
• [Journal Article] DRR1 is expressed in the developing nervous system and downregulated during neuroblastoma carcinogenesis (2010)
  • Author(s): Asano, Y., Kishida, S., Mu, P., Sakamoto, K., Murohara, T., Kadomatsu, K
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 394 Pages: 829-835
  • Peer Reviewed
• [Journal Article] Potential value of human thrombomodulin and DAF expression for coagulation control in pig-to-human xenotransplantation (2010)
  • Author(s): Miwa Y, Yamamoto K, Onishi A, Iwamoto M, Yazaki S, Haneda M, Iwasaki K, Liu D, Ogawa H, Nagasaka T, Uchida K, Nakao A, Kadomatsu K, Kobayashi T
  • Journal Title: Xenotransplantation Volume: 17 Pages: 26-37
  • Peer Reviewed
• [Journal Article] Hyaluronan oligosaccharides promote functional recovery after spinal cord injury in rats (2010)
  • Author(s): Wakao, N., Imagama, S., Tauchi, R., Muramoto, A., Zhang, H., Natori, T., Takeshita, S., Ishiguro, N., Matsuyama, Y., Kadomatsu, K
  • Journal Title: Neurosci. Lett Volume: 488 Pages: 299-304
  • Peer Reviewed
• [Journal Article] Keratan sulfate suppresses cartilage damage and ameliorates inflammation in an experimental mice arthritis model (2010)
  • Author(s): Hayashi M, Kadomatsu K, Ishiguro N
  • Journal Title: Biochem Biophys Res Commun Volume: 401(3) Pages: 463-8
  • Peer Reviewed
• [Journal Article] Midkine Regulation of the Renin-Angiotensin System (2010)
  • Author(s): Kadomatsu, K
  • Journal Title: Curr Hypertens Rep Volume: 12 Pages: 74-79
  • Peer Reviewed
• [Journal Article] Hyaluronan oligosaccharides promote functional recovery after spinal cord injury in rats (2010)
  • Author(s): Wakao, N., Imagama, S., Tauchi, R., Muramoto, A., Zhang, H., Natori, T., Takeshita, S., Ishiguro, N., Matsuyama, Y., Kadomatsu, K.
  • Journal Title: Neurosci.Lett. Volume: 488 Pages: 299-304
  • Peer Reviewed
• [Journal Article] DRR1 is expressed in the developing nervous system and downregulated during neuroblastoma carcinogenesis (2010)
  • Author(s): Asano, Y., Kishida, S., Mu, P., Sakamoto, K., Murohara, T., Kadomatsu, K
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 394 Pages: 829-835
  • 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 Volume: 296 Pages: 462-469
  • Peer Reviewed
• [Journal Article] Transforming growth factor-β1 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 Volume: 1263 Pages: 10-22
  • Peer Reviewed
• [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 Volume: 125 Pages: 2978-2990
  • Peer Reviewed
• [Journal Article] The E-selectin ligand Basigin/CD147 is responsible for neutrophil recruitment in renal ischemia/reperfusion (2009)
  • Author(s): Kato, N., Yuzawa, Y., Kosugi, T., Hobo, A., Sato, W., Miwa, Y., Sakamoto, K., Matsuo, S., Kadomatsu, K
  • Journal Title: J. Am. Soc. Nephrol Volume: 20 Pages: 1565-1576
  • Peer Reviewed
• [Journal Article] The growth factor midkine regulates the renin-angiotensin system in mice (2009)
  • Author(s): Hobo, A., Yuzawa, Y., Kosugi, T., Kato, N., Asai, N., Sato, W., Maruyama, S., Ito, Y., Kobori, H., Ikematsu, S., Akira Nishiyama, A., Matsuo, S., Kadomatsu, K
  • Journal Title: J. Clin. Invest Volume: 119 Pages: 1616-1625
  • Peer Reviewed
• [Journal Article] Disruption of the midkine gene(Mdk) delays degeneration and regeneration in injured peripheral nerve (2009)
  • Author(s): Sakakima H, Yoshida Y, Yamazaki Y, Matsuda F, Ikutomo M, Ijiri K, Muramatsu H, Muramatsu T, Kadomatsu K
  • Journal Title: J Neurosci Res Volume: 87 Pages: 2908-2915
  • Peer Reviewed
• [Journal Article] Successful cross-breeding of cloned pigs expressing endo-beta-galactosidase C and human decay accelerating factor (2009)
  • Author(s): Yazaki S, Iwamoto M, Onishi A, Miwa Y, Suzuki S, Fuchimoto D, Sembon S, Furusawa T, Hashimoto M, Oishi T, Liu D, Nagasaka T, Kuzuya T, Maruyama S, Ogawa H, Kadomatsu K, Uchida K, Nakao A, Kobayashi T
  • Journal Title: Xenotransplantation Volume: 16 Pages: 511-521
  • Peer Reviewed
• [Journal Article] Transforming growth factor-β_1 upregulates keratan sulfate and chondroitin sulfate biosynthesis in microglias after brain injury (2009)
  • Author(s): Yin J., et al.
  • Journal Title: Brain Res. 1263 Pages: 10-22
  • Peer Reviewed
• [Journal Article] The growth factor midkine regulates the renin-angiotensin system in mice (2009)
  • Author(s): Hobo A., et al
  • Journal Title: J Clin Invest. 119 Pages: 1616-1625
  • Peer Reviewed
• [Journal Article] Disruption of the midkine gene (Mdk) delays degeneration and regeneration in injured peripheral nerve (2009)
  • Author(s): Sakakima H., et al.
  • Journal Title: J Neurosci Res 87 Pages: 2908-2915
  • Peer Reviewed
• [Journal Article] The E-selectin ligand basigin/CD147 is responsible for neutrophil recruitment in renal ischemia/reperfusion (2009)
  • Author(s): Kato N., et al.
  • Journal Title: J Am Soc Nephrol. 20 Pages: 1565-1576
  • Peer Reviewed
• [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., et al.
  • Journal Title: Int J Cancer 125 Pages: 2978-2990
  • Peer Reviewed
• [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
  • Peer Reviewed
• [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 Volume: 16 Pages: 387-395
  • Peer Reviewed
• [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 Volume: 7 Pages: 211-221
  • Peer Reviewed
• [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
  • Journal Title: J. Vas. Surg Volume: 47 Pages: 1322-1329
  • Peer Reviewed
• [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 Volume: 99 Pages: 1125-1130
  • NAID: 10024007074
  • Peer Reviewed
• [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 Volume: 107 Pages: 789-798
  • Peer Reviewed
• [Journal Article] Plasma midkine leveli is a prognostic factor for human neuroblastoma (2008)
  • Author(s): Ikematsu, S., Nakagawara, A., Nakamura, Y., Ohira, M., Shinjo, M., Kishida, S., Kadomatsu, K
  • Journal Title: Cancer Sci Volume: 99 Pages: 2070-2074
  • Peer Reviewed
• [Journal Article] Removal of blood group A/B antigen in organs by ex vivo and in vivo administration of ando-β-galactosidase(ABase) for ABO incompatible transplantation (2008)
  • Author(s): Kobayashi, T., Liu, D., Ogawa, H., Miwa, Y., Nagasaka, T., Maruyama. S., Li, Y., Onishi, A., Iwamoto, M., Kuzuya, T., Kadomatsu, K., Uchida, K., Nakao, A
  • Journal Title: Transplant Immunol Volume: 20 Pages: 132-138
  • Peer Reviewed
• [Journal Article] Expression and roles of a xenopus head-forming gene homologue in human cancer cell lines. (2008)
  • Author(s): Zhu, Y., Tsuchida, A., Yamamoto, A., Furukawa, K., Tajima, O., Tokuda, N., Aizawa, S., Urano, T., Kadomatsu, K, Furukawa, K
  • Journal Title: Med. Sci Volume: 70 Pages: 73-82
  • NAID: 110007018287
  • Peer Reviewed
• [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.
  • Journal Title: J. Vas. Surg. 47 Pages: 1322-1329
  • Peer Reviewed
• [Presentation] The role of proteoglycans in neural plasticity (2010)
  • Author(s): Kadomatsu, K
  • Organizer: The 65th west lake international symposium of Zhejiang University
  • Place of Presentation: Hangzhou, China
  • Year and Date: 2010-11-20
• [Presentation] The role of proteoglycans in neural plasticity (2010)
  • Author(s): Kadomatsu, K
  • Organizer: The 65^<th> west lake international symposium of Zhejiang University
  • Place of Presentation: Hangzhou, China(招待講演)
  • Year and Date: 2010-11-20
• [Presentation] Axonal regeneration and proteoglycans (2010)
  • Author(s): Kadomatsu, K
  • Organizer: 28th Naito Conference
  • Place of Presentation: Shonan, Japan
• [Presentation] Midkine : An enigmatic but interesting growth factor (2010)
  • Author(s): Kadomatsu, K
  • Organizer: Excellence in midkine research conference
  • Place of Presentation: Sydney Australia
• [Presentation] Axonal regeneration and proteoglycans (2010)
  • Author(s): Kadomatsu, K
  • Organizer: 28^<th> Naito Conference
  • Place of Presentation: Shonan, Japan(招待講演)
• [Presentation] Midkine : An enigmatic but interesting growth factor (2010)
  • Author(s): Kadomatsu, K.
  • Organizer: Excellence in midkine research conference
  • Place of Presentation: Sydney Australia(招待講演)
• [Presentation] 神経軸索再生とプロテオグリカン (2009)
  • Author(s): 門松健治
  • Organizer: 第32回分子生物学会シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-10
• [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
• [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
• [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
• [Remarks]
  • URL: http://www.med.nagoya-u.ac.jp/biochem/
• [Remarks]
  • URL: http://www.med.nagoya-u.ac.jp/biochem/
• [Patent(Industrial Property Rights)] 急性腎障害及び予後推進用バイオマーカー並びにその用途 (2009)
  • Inventor(s): 門松健治
  • Industrial Property Rights Holder: 法人名大
  • Acquisition Date: 2009-12-18
  • Overseas
• [Patent(Industrial Property Rights)] 神経障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 (2008)
  • Inventor(s): 門松健治
  • Industrial Property Rights Holder: 法人名大
  • Filing Date: 2008-06-30
  • Overseas