2007 Fiscal Year Final Research Report Summary
Effect of siRNA targeting SHP-1 on angiogenesis in hindlimb ischemia
| Project/Area Number |
18590817
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kyushu University |
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Principal Investigator |
SUGANO Masahiro Kyushu University, Medical Institution of Bioregulation, Associate Professor (20206395)
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| Co-Investigator(Kenkyū-buntansha) |
OYAMA Junichi Kyushu University, Hospital, Assistant Professor (30359939)
HIGUCHI Yoshihiro Kyushu University, Mediral Institution, Assistant Professor (40404032)
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| Project Period (FY) |
2006 – 2007
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| Keywords | angiogenesis / tyrosine phosphatases / SHP-1 / genr therapy |
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| 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.
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Research Products
(21 results)
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[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.
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Journal Title
J Neuropsychiatry Clin Neurosci 19
Pages: 342-343
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[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
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Journal Title
Mol Cell Biochem 304
Pages: 353-360
Description
「研究成果報告書概要(欧文)」より
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[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
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Journal Title
J Neuropsychiatry Clin Neurosci 19
Pages: 342-343
Description
「研究成果報告書概要(欧文)」より
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[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
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Journal Title
Int J Cardiol 111
Pages: 405-412
Description
「研究成果報告書概要(欧文)」より
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[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
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Journal Title
Can J Physiol Pharmacol 84
Pages: 443-449
Description
「研究成果報告書概要(欧文)」より
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[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
