Basic research for development of therapeutic strategy against atherosclerosis targeting interendothelial adhesion

• Project/Area Number: 22590828
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kobe University
• Principal Investigator: RIKITAKE Yoshiyuki 神戸大学, 大学院・医学研究科, 准教授 (50419488)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 分子血管病態学 / 動脈硬化 / 接着分子 / 血管新生 / 血管平滑筋細胞 / 血管石灰化 / シグナル伝達 / Necl-5 / 血管内皮細胞 / 血管内皮増殖因子 / Rap1 / アファディン

Research Abstract

Necl-5, an immunoglobulin-like molecule, and afadin, an actin-binding protein, regulated tube formation, migration, proliferation and survival of vascular endothelial cells by controlling VEGF-induced activation of the Rap1-Akt signaling. Angiogenesis following femoral artery excision was reduced in Necl-5-knockout and endothelium-specific afadin-knockout mice. Our study revealed that Necl-5 and afadin in endothelial cells regulate angiogenesis.

Research Products

• [Journal Article] Afadin/AF-6 and Canoe: Roles in cell adhesion and beyond (2013)
  • Author(s): Kenji Mandai
  • Journal Title: Progress in Molecular Biology and Translational Science Volume: 116 Pages: 433-454
  • DOI: 10.1016/b978-0-12-394311-8.00019-4
  • Peer Reviewed
• [Journal Article] FGD5 mediates pro-angiogenic action of vascular endothelial growth factor in human vascular endothelial cells (2012)
  • Author(s): Yusuke Kurogane, Yoshiyuki Rikitake, et al.
  • Journal Title: Arteriosclerosis, Thrombosis, and Vascular Biology Volume: 32巻 Issue: 4 Pages: 988-996
  • DOI: 10.1161/atvbaha.111.244004
  • Peer Reviewed
• [Journal Article] Necl-5/Poliovirus Receptor Interacts with VEGFR2 and Regulates VEGF-induced Angiogenesis. (2012)
  • Author(s): Kinugasa, M. et al.
  • Journal Title: Circ. Res. Volume: 17 Issue: 5 Pages: 716-726
  • DOI: 10.1161/circresaha.111.256834
  • Peer Reviewed
• [Journal Article] Osteoblast-like differentiation of cultured human coronary artery smooth muscle cells by bone morphogenetic protein endothelial cell precursor-derived regulator (BMPER). (2012)
  • Author(s): Satomi-Kobayashi, S.
  • Journal Title: J. Biol. Chem. Volume: 287 Issue: 36 Pages: 30336-30345
  • DOI: 10.1074/jbc.m111.329110
  • Peer Reviewed
• [Journal Article] Immunoglobulin superfamily receptors and adherens junctions. (2012)
  • Author(s): Shimono, Y.
  • Journal Title: Subcell Biochem. Volume: 60 Pages: 137-170
  • DOI: 10.1007/978-94-007-4186-7_7
  • ISBN: 9789400741850, 9789400741867
  • Peer Reviewed
• [Journal Article] The role of nectins in different types of cell-cell adhesion. (2012)
  • Author(s): Rikitake, Y.
  • Journal Title: J Cell Sci. Volume: 125 Issue: 16 Pages: 3713-3722
  • DOI: 10.1242/jcs.099572
  • Peer Reviewed
• [Journal Article] Role of Afadin in Vascular Endothelial Growth Factor- and Sphingosine 1-Phosphate-Induced (2010)
  • Author(s): Hideto Tawa, Yoshiyuki Rikitake, et al
  • Journal Title: Angiogenesis, Circulation Research Volume: 106巻 Issue: 11 Pages: 1731-1742
  • DOI: 10.1161/circresaha.110.216747
  • Peer Reviewed
• [Journal Article] Role of Afadin in Vascular Endothelial Growth Factor- and Sphingosine1-Phosphate-Induced Angiogenesis (2010)
  • Author(s): Hideto Tawa, Yoshiyuki Rikitake, et al.
  • Journal Title: Circulation Research Volume: 106 Pages: 1731-1742
  • Peer Reviewed
• [Presentation] Nectin-like Molecule-5 in Vascular Smooth Muscle Cells Regulates Intimal Thickening in Mice (2012)
  • Author(s): Fumie Kureha, Seimi Kobayashi, Mitsuo Kinugasa, Ken-ichi Hirata, Yoshiyuki Rikitake
  • Organizer: 第76回日本循環器学会総会・学術集会
  • Place of Presentation: 福岡国際会議場(福岡県)
  • Year and Date: 2012-03-17
• [Presentation] Nectin-like Molecule-5 Regulates Formation of Intimal Thickening in Mouse Carotid Artery and Phenotypic Reversion of Vascular Smooth Muscle Cells, Scientific Sessions 2012 (2012)
  • Author(s): Fumie Kureha,et al.
  • Organizer: American Heart association
  • Place of Presentation: Los Angeles, USA
• [Presentation] Necl-5/PVR/CD155, an Immunoglobulin-like Cell Adhesion Molecule, Regulates Vascular Endothelial Growth Factor-Induced Angiogenesis (2012)
  • Author(s): Mitsuo Kinugasa, et al.
  • Organizer: ISA2012
  • Place of Presentation: Sydney, Australia
• [Presentation] Regulation of Intimal Thickening Following Carotid Artery Ligation in Mice by the Immunoglobulin-like Cell Adhesion Molecule Necl-5 (2011)
  • Author(s): Yoshiki Kubo, Fumie Kureha, Seimi Kobayash, Mitsuo Kinugasa, Muneaki Miyata, Jun Miyoshi, Ken-ichi Hirata, Yoshimi Takai, Yoshiyuki Rikitake
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-12-15
• [Presentation] Nectin-like molecule-5 Regulates Vascular Smooth Muscle Proliferation and Migration and Mediates Intimal Thickening in Mice (2011)
  • Author(s): Fumie Kureha, Yoshiki Kubo, Jun Miyoshi, Ken-ichi Hirata, Yoshiyuki Rikitake
  • Organizer: 第19回日本血管生物医学会学術集会
  • Place of Presentation: 東京ステーションコンファレンス(東京都)
  • Year and Date: 2011-12-10
• [Presentation] Regulation of VEGF-induced Pro-angiogenic Activities of Endothelial Cells by FGD5 (2011)
  • Author(s): Yusuke Kurogane, Yohiyuki Rikitake, Tatsuro Ishida, Ken-ichi Hirata
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-08-04
• [Presentation] Necl-5, an Immunoglobulin-like Cell Adhesion Molecule, Regulates VEGF-induced Angiogenesis in Ischemia (2011)
  • Author(s): Mitsuo Kinugasa, Yoshisoiki Rikitake, Yusuke Kurogane, Fumie Kureha, Hideto Tawa, Seimi Kobayashi, Ken-ichi Hirata
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-08-03
• [Presentation] The Immunoglobulin-like Molecule Necl-5/PVR Regulates Vascular Endothelial Growth Factor-Induced Angiogenesis (2011)
  • Author(s): Mitsuo Kinugasa, Yoshiyuki Rikitake, Yusuke Kurogane, Fumie Kureha, Seimi Kobayashi, Ken-ichi Hirata
  • Organizer: 第43回日本動脈硬化学会総会・学術集会
  • Place of Presentation: ロイトン札幌(北海道)
  • Year and Date: 2011-07-15
• [Presentation] FGD5 Regulates VEGF-induced Pro-angiogenic Activities of Endothelial Cells (2011)
  • Author(s): Yusuke Kurogane, Yoshiyuki Rikitake, Muneaki Miyata, Yoshiki Kubo, Yuichi Nagamatsu, Tatsuro Ishida, Thomas Quertermous, Ken-ichi Hirata
  • Organizer: 第43回日本動脈硬化学会総会・学術集会
  • Place of Presentation: ロイトン札幌(北海道)
  • Year and Date: 2011-07-15
• [Presentation] Regulation of Angiogenesis by the Immunoglobulin-like Molecule Necl-5 (2010)
  • Author(s): Muneaki Miyata, Yoshiyuki Rikitake, et al.
  • Organizer: BMB2010(第33回日本分子生物学会年会・第83回日本生化学会大会合同大会)
  • Place of Presentation: 神戸国際会議場(兵庫県)
  • Year and Date: 2010-12-07
• [Presentation] VEGFによる血管新生におけるNecl-5の役割 (2010)
  • Author(s): 衣笠允雄、力武良行、小林成美、銕祐介、平田健一
  • Organizer: 第18回日本血管生物医学会学術集会
  • Place of Presentation: 梅田スカイビル(大阪府)
  • Year and Date: 2010-12-02
• [Presentation] BMPER（BMP-binding endothelial regulator）による血管平滑筋細胞の骨芽細胞様細胞への形質転換
  • Author(s): 小林 成美
  • Organizer: 第12回日本NO学会学術総会
  • Place of Presentation: 神戸国際会議場（神戸市）
• [Presentation] マウス内膜肥厚形成におけるネクチン様分子-5の役割
  • Author(s): 呉羽 布美恵
  • Organizer: 第12回日本NO学会学術総会
  • Place of Presentation: 神戸国際会議場（神戸市）
• [Presentation] VEGFによる血管新生におけるNecl-5の役割
  • Author(s): 衣笠 允雄
  • Organizer: 第12回日本NO学会学術総会
  • Place of Presentation: 神戸国際会議場（神戸市）
• [Presentation] ERK Acts Downstream of Nectin-like Molecule-5 in Phenotypic Reversion of Vascular Smooth Muscle Cells
  • Author(s): Fumie Kureha
  • Organizer: 第77回日本循環器学会総会・学術集会
  • Place of Presentation: パシフィコ横浜（横浜市）
• [Book] Directional Cell Migration: Regulation by Small G Proteins (2011)
  • Author(s): Yoshiyuki Rikitake, Yoshimi Takai, Elsevier, Int Rev Cell Mol Biol.
  • Publisher: Nectin-like Molecule-5, and Afadin
• [Book] Directional Cell Migration : Regulation by Small G Proteins, Nectin-like Molecule-5, and Afadin (2011)
  • Author(s): Yoshiyuki Rikitake, Yoshimi Takai
  • Total Pages: 47
  • Publisher: Elsevier
• [Remarks]
  • URL: http://www.med.kobe-u.ac.jp/sigtra/Signal%20Transduction/Home.html