| Project/Area Number |
09670729
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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 | Nagasaki University |
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Principal Investigator |
SETO Shinji Nagasaki University School of Medicine Hospital, Lecturer, 医学部附属病院, 講師 (00136657)
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| Co-Investigator(Kenkyū-buntansha) |
YAMASHITA Shun-ichi Nagasaki University School of Medicine, Professor, 医学部, 教授 (30200679)
ITOH Masahiro Nagasaki University School of Medicine, Assistant Professor, 医学部, 助教授 (30184691)
ASHIZAWA Naoto Nagasaki University School of Medicine Hospital, Assistant, 医学部附属病院, 助手 (10301368)
YANO Katsusuke Nagasaki University School of Medicine, Professor, 医学部, 教授 (50039864)
OHTSURU Akira Nagasaki University School of Medicine, Assistant, 医学部, 助手 (00233198)
松山 俊文 長崎大学, 医学部, 教授 (30165922)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Receptor-type PTKs / Left ventricular hypertrophy / HGF / c-Met / VEGF / Flt-Flk / Angiopoietin / Tie-Tek / Tek / Flk-1,Flt-1 |
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| Research Abstract |
Activation of protein tyrosine kinases (PTKs) has been postulated to be involved in cell differentiation and proliferation. To elucidate the involvement of tyrosine kinase genes in hypertrophied heart, we analyzed the expression patterns of receptor-type PTKs in the normal and 2 kidney-I clip and DOCA-salt hypertensive hypertrophied heart in the rats. RT-PCR was performed using degenerated primers which were designed from highly conserved regions in the catalytic domains of receptor-type PTKs. To compare the expression level of these PTK mRNAs in the normal and hypertrophied heart, . we performed semi-competitive RT-PCR and immunohistochemical analysis. Nucleotide sequencing of 81 clones of PTKs revealed 10 receptor-type, 5 nonreceptor-type and 2 unknowns in the rat heart. Tie-2/Tek, Ryk, IGF-I receptor were abundantly expressed in the rat heart as a member of receptor-type PTKs. Immunohistochemistry and RT-PCR demonstrated the presence of PDGF-alpha. receptor, PDGF-beta receptor and .FGF-3 receptor in both normal and hypertrophied hearts. We also confirmed the Fit-1, KDR/Flk-1, and their ligand VEGF, c-Met and its ligand HGF, and Tie-1, Tie-2/Tek in the hearts by immunohistochemistry and RT-PCR.The expression of cardiac HGF and c-Met in the hypertrophied hearts especially 2 kidney-I clip rats were strong in protein level. These findings suggest that HGF/c-Met interactions may play an important role not only in angiogenesis but also in cardiac hypertrophy and remodeling.
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