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Effect of siRNA targeting SHP-1 on angiogenesis in hindlimb ischemia

Research Project

Project/Area Number 18590817
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKyushu University

Principal Investigator

SUGANO Masahiro  Kyushu University, Medical Institution of Bioregulation, Associate Professor (20206395)

Co-Investigator(Kenkyū-buntansha) OYAMA Junichi  Kyushu University, Hospital, Assistant Professor (30359939)
HIGUCHI Yoshihiro  Kyushu University, Mediral Institution, Assistant Professor (40404032)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsangiogenesis / tyrosine phosphatases / SHP-1 / genr therapy / 遺伝子治療 / Protein tyrosine phosphatase / angiogenesis / Peripheral ischemic disease / gene therapy
Research Abstract

Vascular endothelial growth factor (VEGF) promotes the growth of vascular endothelial cells and the development of new blood vessels through interaction with VEGF receptor-2 (KDR/flk-1). The binding of VEGF to KDR/flk-1 induces conformational changes in the receptor, followed by dimerization and autophosphorylation of the tyrosine residues. The phosphorylated KDR/flk-1 can be a substrate for intracellular protein tyrosine phosphatases. SHP-1 , a cytoplasmic protein tyrosine phosphatase that contain two Src homology 2 domains in its N-terminal half, interacts with activated cytokine, growth factor, and antigen receptors and plays a negative regulatory role in signal transduction pathways by dephosphorylation of the receptors or receptor substrates to which it binds. Thus, therapeutic angiogenesis designed to inhibit expression of SHP-1 would be beneficial in hindlimb ischemia. Here we report that siRNA targeting SHP-1 activates KDR/flk-1 and accelerates angiogenesis in a rat model of hindlimb ischemia. Upon injection to the ischemic adductor muscle, vector-based siRNA reduced SHP-1, increased phosphorylation of KDR/flk-1, and markedly increased capillary density. Our data demonstrate in vivo the potential use of siRNA targeting SHP-1 as therapy for peripheral ischemic diseases.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (28 results)

All 2007 2006

All Journal Article (19 results) (of which Peer Reviewed: 7 results) Presentation (9 results)

  • [Journal Article] SiRNA targeting SHP-1 accelerates angiogenesis in a rat model of hindl imb ischemia2007

    • Author(s)
      Sugano M, Tsuchida K, Maeda T, Makino N.
    • Journal Title

      Atherosclerosis 191

      Pages: 33-39

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Change in telomere length distribution in the Japanese population2007

    • Author(s)
      Guan JZ, Maeda T, Sugano M, Oyama J, Higuchi Y, Makino N.
    • Journal Title

      Mol Cell Biochem 304

      Pages: 353-360

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Familial Turner mosaicism 46XX/45XO with brain calcification2007

    • Author(s)
      Maeda T, Sugano M, Guan JZ, Oyama J, Higuchi Y, Makino N, Hatakenaka M, Muta H, Nakayama M, Nakazaki Y, Kurita R, Hiroyama T, Suzuki T, Tani K.
    • Journal Title

      J Neuropsychiatry Clin Neurosci 19

      Pages: 342-343

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] SiRNA targeting SHP-1 accelerates angiogenesis in a rat model of hindlimb ischemia2007

    • Author(s)
      Sugano, M, Tsuchida, K, Maeda, T, Makino, N
    • Journal Title

      Atherosclerosis 191

      Pages: 33-39

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Change in telomere length distribution in the Japanese population2007

    • Author(s)
      Guan, JZ, Maeda, T, Sugano, M, Oyama, J, Higuchi, Y, Makino, N
    • Journal Title

      Mol Cell Biochem 304

      Pages: 353-360

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Familial Turner mosaicism 46XX/45XO with brain calcification2007

    • Author(s)
      Maeda, T, Sugano, M, Guan, JZ, Oyama, J, Higuchi, Y, Makino, N, Hatakenaka, M, Muta, H, Nakayama, M, Nakazaki, Y, Kurita, R, Hiroyama, T, Suzuki, T, Tani, K
    • Journal Title

      J Neuropsychiatry Clin Neurosci 19

      Pages: 342-343

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Change in telomere length distribution in the Japanese population2007

    • Author(s)
      Guan JZ, Maeda T, Sugano M, Oyama J, Higuchi Y, Makino N.
    • Journal Title

      Mol Cell Biochem. 304

      Pages: 353-360

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SiRNA targeting SHP-1 accelerates angiogenesis in a rat model of hindlimb ischemia.2007

    • Author(s)
      Sugano M, Tsuchida K, Maeda T, Makino N.
    • Journal Title

      Atherosclerosis. 19(1)

      Pages: 33-39

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Familial Tuner mosaicism 46XX/45XO with brain calcification.2007

    • Author(s)
      Maeda T, Hatakenaka M, Sugano M, Guan JZ, 8名 Makino N.
    • Journal Title

      J. Neuropsychiat. Clin. Neurosci. (印刷中)(in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Peroxisome proliferator-activated receptorgamma ligands attenuate brain natriuretic peptide production and affect remodeling in cardiac fibroblasts in reoxygenation after hypoxia2006

    • Author(s)
      Makino N, Sugano M, Satoh S, Oyama J, Maeda T.
    • Journal Title

      Cell Biochem Biophys 44

      Pages: 65-71

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Increased productivity of tumor necrosis factor-alpha in helper T cells in patients with systolic heart failure2006

    • Author(s)
      Satoh S, Oyama JI, Suematsu N, Kadokami T, Shimoyama N, Okutsu M, Inoue T, Sugallo M, Makino N.
    • Journal Title

      Int J Cardiol 111

      Pages: 405-412

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Somatic DNA recombination in a mouse genomic region,BC-1,in brain and non-brain tissue2006

    • Author(s)
      Maeda T, Mizuno R, Sugano M, Satoh S, Oyama J, Sakoda S, Suzuki T, Makino N.
    • Journal Title

      Can J Physiol Pharmacol 84

      Pages: 443-449

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Peroxisome proliferator-activated receptor-gamma ligands attenuate brain natriuretic peptide production and affect remodeling in cardiac fibroblasts in reoxygenation after hypoxia2006

    • Author(s)
      Makino, N, Sugano, M, Satoh, S, Oyama, J, Maeda, T
    • Journal Title

      Cell Biochem Biophys 44(1)

      Pages: 65-71

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Increased productivity of tumor necrosis factor-alpha in helper T cells in patientswith systolic heart failure2006

    • Author(s)
      Satoh, S, Oyama, JI, Suematsu, N, Kadokami, T, Shimoyama, N, Okutsu, M, Inoue, T, Sugano, M, Makino, N
    • Journal Title

      Int J Cardiol 111

      Pages: 405-412

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Somatic DNA recombination in a mouse genomic region, BC-1, in brain and non-brain tissue2006

    • Author(s)
      Maeda, T, Mizuno, R, Sugano, M, Satoh, S, Oyama, J, Sakoda, S, Suzuki, T, Makino, N
    • Journal Title

      Can J Physiol Pharmacol 84

      Pages: 443-449

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Somatic DNA recombination in a mouse genomic region, BC-1, in brain and non-brain tissue.2006

    • Author(s)
      Maeda T, Mizuno R, Sugano M, Satoh S, Oyama J, Sakoda S, Suzuki T, Makino N.
    • Journal Title

      Can J Physiol Pharmacol. 84(3-4)

      Pages: 443-449

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Transient receptor potential (TRP) protein 7 acts as a G protein-activated Ca(2+) channel mediating angiotensin II-induced myocardial apoptosis.2006

    • Author(s)
      Satoh S, Ranaka H, Ueda Y, Oyama J, Sugano M, Sumimoto H, Mori Y, Makino N.
    • Journal Title

      Mol Cell Biochem. 294 (1-2)

      Pages: 205-215

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Peroxisome proliferator-activated receptor-gamma ligands attenuate brain natriuretic peptide production and affect remodeling in cardiac fibroblasts in reoxy genation after hypoxia.2006

    • Author(s)
      Makino N, Sugano M, Satoh S, Oyama J, Maeda T.
    • Journal Title

      Cell Biochem Biophys. 44(1)

      Pages: 65-71

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Increased productivity of tumor necrosis factor-alpha in helper T cells in patients with systolic heart failure.2006

    • Author(s)
      Satoh S, Oyama J, Suematsu N, Kadokami T, Shimoyama N, Okutsu M, Inoue T, Sugano M, Makino N.
    • Journal Title

      Int J Cardiol. 111(3)

    • Related Report
      2006 Annual Research Report
  • [Presentation] In vivo gene transfer of SHP-1 siRNA alleviates infarct size following is chemia-reperfusion injury2007

    • Author(s)
      Masahiro Sugano, Tomoji Hata, Keiko Tsuchida, and Naoki Makino.
    • Organizer
      The 80th Scientific Sessions of American Heart Association
    • Place of Presentation
      Orlando,USA.
    • Year and Date
      2007-11-07
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] In vivo gene transfer of SHP-1 siRNA alleviates infarct size following ischemiareperfusion injury2007

    • Author(s)
      Sugano, Masahiro, Tomoji, Hata, Keiko, Tsuchida, Naoki, Makino
    • Organizer
      The 80th Scientific Sessions of American Heart Association, (Orlando)
    • Place of Presentation
      USA
    • Year and Date
      2007-11-07
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] SiRNA-mediated inhibition of SHP-1 alleviates infarct size following ischemia-reperfusion injury2007

    • Author(s)
      Masahiro Sugano, Tomoji Hata, Keiko Tsuchida, Toyoki Maeda, Ybshihiro Higuchi, Jun-ichi Oyama, Noki Makino.
    • Organizer
      ESC Congress 2007
    • Place of Presentation
      Vienna
    • Year and Date
      2007-09-05
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] 心筋の虚血再灌流障害におけるSHP-1の影響とSHP-1 siRNAによる予防効果2007

    • Author(s)
      菅野 公浩、畑 知二、土田 啓子、牧野 直樹
    • Organizer
      第11回日本適応学会
    • Place of Presentation
      札幌
    • Year and Date
      2007-06-09
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 心筋の虚血再灌流障害におけるSHP-1の影響とSHP-1siRNAによる予防効果2007

    • Author(s)
      菅野, 公浩, 畑, 知二, 土田, 啓子, 牧野, 直樹
    • Organizer
      第11回日本適応学会
    • Place of Presentation
      札幌
    • Year and Date
      2007-06-09
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] The effect of SHP-1 on infarct size in acute myocard ialinfarction2006

    • Author(s)
      Masahiro Sugano
    • Organizer
      International Academy of Cardiovascular Science, 2nd World Congress, Symposium Session
    • Place of Presentation
      Sapporo
    • Year and Date
      2006-07-16
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ラット下肢虚血モデルにおけるsHP-1の影響とSHP-1 siRNAによる予防効果2006

    • Author(s)
      菅野 公浩、土田 啓子、前田 豊樹、尾山 純一、樋口 義洋、牧野 直樹
    • Organizer
      第10回日本適応学会
    • Place of Presentation
      東京
    • Year and Date
      2006-06-23
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ラット下肢虚血モデルにおけるSHP-1の影響とSHP-1 siRNA による予防効果2006

    • Author(s)
      菅野, 公浩, 土田, 啓子, 前田, 豊樹, 尾山, 純一, 樋口, 義洋, 牧野, 直樹
    • Organizer
      第10回日本適応学会
    • Place of Presentation
      東京
    • Year and Date
      2006-06-23
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The effect of SHP-1 on infarct size in acute myocardial infarction2006

    • Author(s)
      Masahiro, Sugano
    • Organizer
      International Academy of Cardiovascular Science, 2nd World Congress, Symposium Session
    • Place of Presentation
      Sapporo, Japan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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