Molecular mechanisms of postnatal angiogenesis and neurogenesis

2013 Fiscal Year Final Research Report

• Project/Area Number: 23249020
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Nagoya University
• Principal Investigator: TAKAHASHI Masahide 名古屋大学, 医学(系)研究科(研究院), 教授 (40183446)
• Co-Investigator(Kenkyū-buntansha): ENOMOTO Atsushi 名古屋大学, 医学系研究科, 准教授 (20432255) ; ASAI Naoya 名古屋大学, 医学系研究科, 准教授 (80273233) ; MURAKUMO Yoshiki 北里大学, 医学部, 教授 (40324438)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: Girdin / Akt / 細胞運動 / 神経新生 / 血管新生

Research Abstract

To identify the cellular population responsible for the phenotype of girdin KO mice, newly generated girdin flox mice were crossed with nestin-promoter driven Cre-transgenic mice to obtain girdin conditional knockout mice.Our findings suggested that girdin expression in nestin cell lineage is responsible for the phenotype of girdin KO mice.
We used a mouse model of pathological ocular neovascularization: oxygen-induced retinopathy.Pathological neovascularization was decreased in S1416A knockin mice. The results demonstrate that girdin and its phosphorylation play an important role in neonatal vascular development and in pathological neovascularization in the retina.We also found that depletion of girdin attenuated venous smooth muscle cells migration and proliferation in vitro and intimal hyperplasia in vein grafts in vivo.
Moreover, we demonstrated that a girdin family protein, Dishevelled-associating protein Daple, controls the non-canonical Wnt/Rac pathway and cell motility

Research Products

• [Journal Article] The impact of Girdin expression on recurrence-free survival in patients with luminal-type breast cancer (2014)
  • Author(s): Nishimae K., Tsunoda, N., Yokoyama, Y., Kokuryo, T., Iwakoshi, A., Takahashi, M. and Nagiono, M.
  • Journal Title: Breast Cancer Volume: (in press)
  • Peer Reviewed
• [Journal Article] Role of Girdin in intimal hyperplasia in vein grafts and efficacy of atelocollagen-mediated application of siRNA for vein failure (2014)
  • Author(s): Miyachi, H., Mii, S., Enomoto, A., Murakumo, Y., Kato, T., Asai, N., Komori, K. and Takahashi, M.
  • Journal Title: J. Vasc. Surg. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Proteomic analysis of Girdin-interacting proteins in migrating new neurons in the postnatal mouse brain (2013)
  • Author(s): Ota, H., Hikita, T., Nishioka, T., Matsumoto, M., Ito, J., Asai, N., Enomoto, A., Takahashi, M., Kaibuchi, K., Sobue, K. and Sawamoto, K.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 442 Pages: 16-21
  • Peer Reviewed
• [Journal Article] Girdin and its phosphorylation dynamically regulate neonatal vascular development and pathological neovascularization in the retina (2013)
  • Author(s): Ito, T., Komeima, K., Yasuma, T., Enomoto, A., Asai, N., Iwase, S., Takahashi, M. and Terasaki, H.
  • Journal Title: Am. J. Pathol. Volume: 182 Pages: 586-596
  • Peer Reviewed
• [Journal Article] Girdin locates in centrosome and midbody and plays an important role in cell division (2012)
  • Author(s): Mao, J.-Z., Jiang, P., Cui, S.-P., Ren, Y.-L., Zhao, J., Yin, X.-H., Enomoto, A., Liu, H.-J., Hou, L., Takahashi, M. and Zhang, B.
  • Journal Title: Cancer Sci. Volume: 103 Pages: 1780-1787
  • Peer Reviewed
• [Journal Article] Similar Phenotypes of Girdin germ-line and conditional knockout mice indicate a crucial role for Girdin in the nestin lineage (2012)
  • Author(s): Asai M., Asai, N., Murata, A., Yokota, H., Ohmori, K., Mii, S., Enomoto, A., Murakumo, Y. and Takahashi, M.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 426 Pages: 533-538
  • Peer Reviewed
• [Journal Article] The Dishevelled-associating protein Daple controls the non-canonical Wnt/Rac pathway and cell motility (2012)
  • Author(s): Ishida-Takagishi, M., Enomoto, A., Asai, N., Ushida, K., Watanabe, T., Hashimoto, T., Kato, T., Weng, L., Matsumoto, S., Asai, M., Murakumo, Y., Kaibuchi, K., Kikuchi, A. and Takahashi, M.
  • Journal Title: Nature Commun. Volume: May 29 3 Pages: 859
  • Peer Reviewed
• [Journal Article] Involvement of Girdin in the determination of cell polarity during cell migration (2012)
  • Author(s): Ohara, K., Enomoto, A., Kato, T., Hashimoto, T., Isotani-Sakakibara, M., Asai, N., Ishida,-Takagishi, M., Weng, L., Nakayama, M., Watanabe, T., Kato, K., Kaibuchi, K., Murakumo, Y., Hirooka, Y., Goto, H. and Takahashi M.
  • Journal Title: PLoS One Volume: 7 Pages: e36681
  • Peer Reviewed
• [Journal Article] Girdin maintains the stemness of glioblastoma stem cells (2012)
  • Author(s): Natsume, A., Kato, T., Kinjo, S., Enomoto, A., Toda, H., Shimato, S., Ohka, F., Motomura, K., Kondo, Y., Miyata, T., Takahashi, M. and Wakabayashi, T.
  • Journal Title: Oncogene Volume: 31 Pages: 2715-2724
  • Peer Reviewed
• [Journal Article] Girdin is an intrinsic regulator of neuroblast chain migration in the rostral migratory stream of the postnatal brain (2011)
  • Author(s): Wang, Y., Kaneko, N., Asai, N., Enomoto, A., Isotani-Sakakibara, M., Kato, T., Asai, M., Murakumo, Y., Ota, H., Hikita, T., Namba, T., Kuroda, K., Kaibuchi, K., Ming, G., Song, H., Sawamoto, K. and Takahashi, M.
  • Journal Title: J. Neurosci. Volume: 31 Pages: 8109-8122
  • Peer Reviewed
• [Journal Article] The actin-binding protein Girdin and its Akt-mediated phosphorylation regulate neointima formation after vascular injury (2011)
  • Author(s): Miyake, H., Maeda, K., Asai, N., Shibata, R., Ichimiya, H., Isotani-Sakakibara, M., Yamamura, Y., Kato, K., Enomoto, A., Takahashi, M. and Murohara, T.
  • Journal Title: Circ. Res. Volume: 108 Pages: 1170-1179
  • Peer Reviewed
• [Presentation] Roles of the Akt substrate Girdin in cancer progression and angiogenesis (2014)
  • Author(s): Takahashi, M., Enomoto, A. and Asai, N.
  • Organizer: International Symposium on Nanomedicine
  • Place of Presentation: Nagoya University Graduate School of Medicine, Nagoya
  • Year and Date: 20140113-14
• [Presentation] Roles of the Akt substrate Girdin in cell motility (2013)
  • Author(s): Takahashi, M.
  • Organizer: 1st International Symposium on Protein Modifications in Pathogenic Dysregulation of Signaling
  • Place of Presentation: The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo
  • Year and Date: 20130201-02
• [Presentation] Roles of the Akt substrate Girdin in cancer progression and angiogenesis (2013)
  • Author(s): Takahashi, M.
  • Organizer: Joint meeting of the Medical School of Nagoya University and the University of Adelaide
  • Place of Presentation: The University of Adelaide, Adelaide, Australia
  • Year and Date: 2013-05-27
• [Presentation] Roles of the Akt substrate Girdin in tumor progression, angiogenesis and neurogenesis (2013)
  • Author(s): Takahashi, M.
  • Organizer: Joint meeting of the Medical School of Nagoya University and the Medical University of Vienna
  • Place of Presentation: Center for Brain Research, Medical University of Vienna, Vienna, Austria
  • Year and Date: 2013-01-28
• [Presentation] Roles of the Akt substrate Girdin in cancer progression, angiogenesis and Neurogenesis (2012)
  • Author(s): Takahashi, M.
  • Organizer: Global Center of Excellence (COE) Program, The 4th International Symposium: Global COE symposium on Neuro-Tumor Biology and Medicine
  • Place of Presentation: Westin Nagoya Castle, Nagoya
  • Year and Date: 20121115-16
• [Presentation] Roles of the Akt substrate Girdin in cancer progression and angiogenesis (2011)
  • Author(s): Takahashi, M.
  • Organizer: Global Center of Excellence (COE) Program, The 3rd International Symposium: New trends in basic and clinical cancer research for innovative Therapy
  • Place of Presentation: Midland Hall, Nagoya
  • Year and Date: 20111208-09
• [Remarks]
  • URL: http://www.med.nagoya-u.ac.jp/patho2/