• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2001 Fiscal Year Final Research Report Summary

Molecular mechanism of vascular formation

Research Project

Project/Area Number 09281101
Research Category

Grant-in-Aid for Scientific Research on Priority Areas (A)

Allocation TypeSingle-year Grants
Research InstitutionTohoku University

Principal Investigator

SATO Yasufumi  Institute of Development, Aging and Cancer, Tohuku University, Professor, 加齢医学研究所, 教授 (50178779)

Co-Investigator(Kenkyū-buntansha) MITSUI Yoji  National Institute of Bioscience and Human-Technology, the chief investigator, 主席研究官
NISHIKAWA Shin-ichi  Kyoto University, Professor, 大学院・医学研究科, 教授 (60127115)
SHIBUYA Masabumi  University of Tokyo, Institute of Medical Science, Professor, 医科学研究所, 教授 (10107427)
FUJIWARA Keigi  National Cardiovascular Center Research Institute, the chief investigator, 循環器形態部長 (10190092)
TSUKITA Shoichirou  Kyoto University, Professor, 大学院・医学研究科, 教授 (50155347)
Project Period (FY) 1997 – 2000
KeywordsEts-1 / Apoptosis / VEGF / Signal Transduction / ES Cell / differentiation / Claudin-5 / Telomerase
Research Abstract

(1) Transient overexpression of transcription factor Ets1 promoted apoptosis of endothelial cells (Ecs). Ets1 increased expression of pro-apoptotic Bid, cytochrome p450, caspase-4, p27 and p21 more than 2 fold, while it decreased expression of anti-apoptotic DAD-1, AXL, Cox-2, IAP-2, and MDM-2 less than 0. 5 fold in Ecs. (2) The signal transduction pathway of VEGF appeared to be different between ECs of large vessels and small vessels. Especially, Ras played an important role in ECs of small vessels. (3) Transgenic mouse experiment revealed that VEGF-E, a new member of VEGF family, promoted angiogenesis without any evidences of vascular permeability. (4) Autophosphorylation sites of VEGFR-2 (KDR) were determined to be 1175Y and 1214Y. Carboxyl-terminal SH2 domain of PLC-γ bound to phosphorylated 1214Y, which was indispensable for the MAPK activation and augmented DNA synthesis. (5) MadCAM-1 was specifically expressed in venous ECs in the early embryonic stage. BMP-4 increased the number of MadCAM-1 positive venous ECs. (6) GFP-tagged genes were stably introduced into mouse embryonic stem (ES) cells. Time-rap video system was established to analyze the differentiation of ES cells and the expression pattern of GFP-tagged genes. (7) Target destruction of claudin-5, and EC-specific claudin, was established. (8) Human TERT gene and SV40 T antigen gene were introduced into human umbilical vein ECs (HUVECS). The table transfectants exhibited the prolongation of cell-division capability and were suggested to produce a novel autocrine growth factor.

  • Research Products

    (76 results)

All Other

All Publications (76 results)

  • [Publications] Tanaka, M., et al.: "Expression of the 37-IDa laminin binding protein in murine lung tumor cell correlates with tumor angiogenesis"Cancer Lett.. 153. 161-168 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanno, S., et al.: "Roles of two VEGF receptor,Flt-1 and KDR,in the signal transduction of VEGF effects in human vascular endothelial cells"Oncogine. 19. 2138-2146 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sato, Y., et al.: "Properties of two VEGF receptors,Flt-1 and KDR,in signal transduction"Ann.N.Y.Acad.Sci.. 902. 201-207 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakano, T., et al.: "Angiogenesisi inhibition by transdominant mutant Ets-1"J.Cell.Ohysiol.. 184. 255-262 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sato, Y., et al.: "Molecular mechanism of angiogenesis transcription factors and their therapeutic relevance"Pharmacol.Ther.. 87. 51-60 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sato, Y., et al.: "Signal transduction and transcriptional of angiogenesis"Ade.Exp.Med.Biol.. 476. 109-115 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sato, Y.: "Role of ETS family transcription factors in vascular development and angiogenesis"CellStruct.Funct.. 26. 19-24 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Teruyama, K., et al.: "Role of transcription factor Ets-1 in the apotosis of human vascular endothelial cells"J.Cell.Physiol.. 188. 243-252 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yashima, R., et al.: "Heterogeneity of the signal transduction pathways for VEGF-induced MAPKs activation in human vascular endothelial cells"J.Cell.Physiol.. 188. 201-210 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Maru, Y., et al.: "An oncogenic form of the Flk-1 kinase has a tubulogenic potential in a sinusoidal endothelial cell line"Eur.J.cell Biol.. 79. 130-143 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chen, H., et al.: "Inhibition of vascular endothelial growth factor activity by transfection with the soluble FLT-1 gene"J.Cardiovasc.Pharmacol.. 36. 498-502 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Maeda, Y., et al.: "Adeno-associated virus-mediated vascular endothelial growth factor gene transfer into cardiac myocytes"J.Cardiovasc.Pharmacol. 36. 438-443 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sawano, A., et al.: "Vascular Endothelial Growth Factor Receptor-1(Flt-1)is a Novel Cell Surface Marker for the Lineage of Monocyte-Macrophages in Humans"Blood. 97. 785-791 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi, T., et al.: "The overexpression of PKCd is involved in vascular endothelial growth factor-resistant apoptosis in cultured primary sinusoidal endothelial cells"Biochem.Biophys.Res.Commun.. 280. 415-420 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiratsuka, S., et al.: "Involvement of Flt-1 Tyrosine Kinase(Vascular Endothelial Growth Factor Receptor-1)in Pathological Angiogenesis"Cancer Res.. 61. 1207-1213 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Luo, J.-C., et al.: "A variant of nuclear localization signal of bipartite-type is required for the nuclear translocation of hypoxia inducible factors(1a,2a and 3a)"Oncogene. 20. 1435-1444 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shibuya, M.: "Structure and dual function of vascular endothelial growth factor receptor-1(Flt-1)"Int.J.Biochem.Cell Biol.. 33. 409-420 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsukita, S.h., et al.: "Pores in the wall: Claudins constitute tight junction strands containing aqueous pores"J.Cell Biol.. 149. 13-16 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fujita, K., et al.: "Clostridium perfringens enterotoxin binds to the second extracellular loop of claudin-3,a tight junction integral membrane protein"FEBS Lett.. 476. 258-261 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sitou, M., et al.: "Complex phenotype of mice lacking occludin,a component of tight junction strands"Mol.Cell Biol.. 11. 4131-4142 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsukita, Sh.: "Tight junctions involving occludin and claudins"Cornea. 19. S142-145 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsukita, S.h., et al: "The structure and function of claudins,cell adhesion molecules at tight junctions"Ann.NY Acad.Sci.. 915. 129-135 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Furuse, M., et al.: "Conversion of Zonula Occludens from tight to leaky strand type by introducing claudin-2 into MDCK I cells"J.Cell Biol.. 153. 263-272 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsukita, Sh., et al.: "Multifunctional strands of tight junctions"Nature Review(Mol.Cell Biol.). 2. 285-293 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka, Y., et al.: "Endothelin-1 is involved in the growth promotion of vascular smooth muscle cells by hyaluronic acid"Int.J.Cardiol.. 76. 39-47 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kaul, S.C., et al.: "Transcriptional inactivation of p53 by deletions and single amino acid changes in mouse mot-1 protein"Biochem.Biophys.Res.Commun.. 279. 602-606 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishikawa, S.I., et al.: "All B cells are progeny of endothelial cells: a new perspective"Immunol Rev.. 175. 112-119 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kubo, H., et al.: "Vascular Endothelial Growth Factor Receptor-3 is essential for maintenance of integrity of endothelial cell lining during tumor angiogenesis"Blood. 96. 546-553 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamashita, J., et al.: "Embryonic stem cell derived Flk 1-positive cells serve as vascular progenitors"Nature. 408. 92-96 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nagaoka, H., et al.: "Ras mediated effector patheways responsible for pre-B cell survival,which is essential for the developmental progression to the late pre-B cell stage"J.Exp.Med.. 192. 171-181 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yokomizo, T., et al.: "Requirement of Runx1/AML1/PEBP2B for the generation of hematopoietic and endothelial cells"Genes to Cells. 6. 13-24 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hemmi, H., et al.: "Temporal and spatial localization of osteoclasts in colonies from embryonic stem cells"Biochem.Biophys.Res.Commun.. 280. 526-534 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Stacker, S.A., et al.: "Vascular endothelial growth factor-D promotes tumor growth and spread via the lymphatics"Nature Med.. 7. 186-191 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Makinen, T., et al.: "Inhibition of lymphangiogenesis and lymphedema in transgenic mice expressing soluble VEGF receptor 3"Nature Med.. 7. 199-205 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwasaka-Yagi, C., et al.: "TGF-□ Attenuates the transactivation activity of Ets-1 despite its induction via the inhibition of DNA binding"Tohoku J.Exp.Med.. 193. 311-318 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Igarashi, T., et al.: "Retinoic acids repress the expression of ETS-1"Tohoku J.Exp.Med.. 194. 35-43 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Teruyama, K., et al.: "Neuropilin-1 is a downstream target of transcription factor Ets-1 in human umbilical vein endothelial cells"FEBS Lett.. 504. 1-4 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shibuya, M.: "Development of the liver vascular system,in Morphogenesis of Endothelium"edited by W.Risau,and G.M.Rubanyi,Harwood Academic Publishers. 175-188 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka M., et al.: "Expression of the 37-kDa laminin binding protein in murine lung tumor cell correlates with tumor angiogenesis."Cancer Lett.. 153. 161-168 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kanno S., et al.: "Roles of two VEGF receptors, Flt-1 and KDR, in the signal transduction of VEGF effects in human vascular endothelial cells."Oncogene. 19. 2138-2146 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sato Y., et al.: "Properties of two VEGF receptors, Flt-1 and KDR, in the signal transduction."Ann. N. Y. Acad. Sci.. 901. 201-207 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakano T., et al.: "Angiogenesis Inhibition by Transdominant Mutant Ets-1."J. Cell. Physiol.. 184. 255-262 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sato Y., et al.: "Molecular mechanism of angiogenesis : transcription factors and their therapeutic relevance."Pharmacol. Ther.. 87. 51-60 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sato Y., et al.: "Signal transduction and transcriptional regulation of angiogenesis."Adv. Exp. Med. Biol.. 476. 109-115 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sato Y., et al.: "Role of ETS family transcription factors in vascular development and angiogenesis."Cell Struct. Funct.. 26. 19-24 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Teruyama K., et al.: "Role of transcription factor Ets-1 in the apoptosisof human vascular endothelial cells."J. Cell. Physiol.. 188. 243-252 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yashima R., et al.: "Heterogeneity of the signal transduction pathways for VEGF-indued MAPKs activation in human vascular endothelial cells."J. Cell. Physiol.. 188. 201-210 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwasaka-Yagi, C., et al.: "TGF-・ Attenuates the transactivation activity of Ets-1 despite its induction via the inhibition of DNA binding."Tohoku J. Exp. Med.. 193. 311-318 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Igarashi, T., et al.: "Retinoic acids repress the expression of ETS-1."Tohoku J. Exp. Med.. 194. 35-43 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Teruyama, K., et al.: "Neuropilin-1 is a downstream target of transcription factor Ets-1 in human umbilical vein endothelial cells."FEBS Lett.. 504. 1-4 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Maru, Y., et al.: "An oncogenic form of the Flt-1 kinase has a tubulogenic potential in a sinusoidal endothelial cell line."Eur. J. Cell Biol.. 79. 130-143 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chen, H., et al.: "Inhibition of vascular endothelial growth factor activity by transfection with the soluble FLT-1 gene."Cardiovasc Pharmacol. 36. 498-502 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Maeda, Y., et al.: "Adeno-associated virus-mediated vascular endothelial growth factor gene transfer into cardiac myocytes."Cardiovasc Pharmacol.. 36. 438-443 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sawano, A., et al.: "Vascular Endothelial Growth Factor Receptor-1 (Flt-1) is a Novel Cell Surface Marker for the Lineage of Monocyte-Macrophages in Humans."Blood. 97. 785-791 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi, T., et al.: "The overexpression of PKCd is involved in vascular endothelial growth factor-resistant apoptosis in cultured primary sinusoidal endothelial cells."Biochem Biophys Res Commun. 280. 415-420 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiratsuka, S., et al.: "Involvement of Flt-1 Tyrosine Kinase (Vascular Endothelial Growth Factor Receptor-1) in Pathological Angiogenesis."Cancer Res.. 61. 1207-1213 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Luo, J. -C., et al.: "A variant of nuclear localization signal of bipartite-type is required for the nuclear translocation of hypoxia inducible factors (1a, 2a and 3a)."Oncogene. 20. 1435-1444 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shibuya, M.: "Structure and dual function of vascular endothelial growth factor receptor-1 (Flt-1)."Int. J. Biochem. Cell Biol.. 33. 409-420 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsukita, Sh., et al.: "Claudins constitute tight junction strands containing aqueous pores."J. Cell Biol.. 149. 13-16 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujita, K., et al.: "Clostridium perfringens enterotoxin binds to the second extracellular loop of claudin-3, a tight junction integral membrane protein."FEBS Lett.. 476. 258-261 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sitou, M., et al.: "Complex phenotype of mice lacking occludin, a component of tight junction strands."Mol. Cell Biol.. 11. 4131-4142 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsukita, Sh.: "Tight junctions involving occludin and claudins."Cornea,. 19. S142-145 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsukita, Sh., et al.: "The structure and function of claudins, cell adhesion molecules at tight junctions."Ann. NY Acad. Sci.. 915. 129-135 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Furuse, M., et al.: "Conversion of Zonula Occludens from tight to leaky strand type by introducing claudin-2 into MDCK I cells."J. Cell Biol.. 153. 263-272 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsukita, Sh., et al.: "Multifunctional strands of tight junctions."Nature Review (Mol. Cell Biol. ). 2. 285-293 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka, Y., et al.: "Endothelin-1 is involved in the growth promotion ofvascular smooth muscle cells by hyaluronic acid."Int J Cardiol. 76. 39-47 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kaul, SC., et al.: "Transcriptional inactivation of p53 by deletions and single amino acid changes in mouse mot-1 protein."Biochem Biophys Res Commun. 279. 602-606 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishikawa, SI., et al.: "All B cells are progeny of endothelial cells : a new perspective."Immunol Rev.. 175. 112-119 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kubo, H., et al.: "Vascular Endothelial Growth Factor Receptor-3 is essential for maintenance of integrity of endothelial cell lining during tumor angiogenesis"Blood. 96. 546-553 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamashita, J., et al.: "Embryonic stem cell derived Flk1-positive cells serve as vascular progenitors."Nature. 408. 92-96 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagaoka, H., et al.: "Ras mediated effector patheways responsible for pre-B cell survival, which is essential for the developmental progression to the late pre-B cell stage."J. Exp. Med.. 192. 171-181 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yokomizo, T., et al.: "Requirement of Runx1/AML1/PEBP2B for the generation of hematopoietic and endothelial cells."Genes to Cells. 6. 13-24 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hemmi, H., et al.: "Temporal and spatial localization of osteoclasts in colonies from embryonic stem cells."Biochem Biophy Res Commu.. 280. 526-534 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Stacker, SA., et al.: "Vascular endothelial growth factor-D promotes tumor growth and spread via the lymphatics."Nature Med. 7. 186-191 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Makinen, T., et al.: "Inhibition of lymphangiogenesis and lymphedema in transgenic mice expressing soluble VEGF receptor 3."Nature Med. 7. 199-205 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shibuya, M.: "Development of the liver vascular system, in Morphogenesis of Endothelium, edited by W. Risau, and G. M. Rubanyi"Harwood Academic Publishers. 175-188 (2000)

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2003-09-17  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi