| Project/Area Number |
09470170
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 |
UENO Hikaru Kyushu Univ., Dept. of Cardiovasc Med., Assoc. Prof., 医学部, 講師 (50260378)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIDA Takahiro Kyushu Univ., Dept. of Cardiovasc Surg, Asssist. Prof., 医学部, 助手 (50284500)
OHHARA Yhuichi Kyushu Univ., Dept. of Cardiovasc Med., Asssist. Prof., 医学部, 助手 (90185364)
TSUTSUI Hiroyuki Kyushu Univ., Dept. of Cardiovasc Med., Asssist. Prof., 医学部, 助手 (70264017)
SUEISHI Katsuo Kyushu Univ., Dept. of Pathol., Prof., 大学院・医学系研究科, 教授 (70108710)
MORI Eizou Toukai Univ., Dept. of Med., Assoc. Prof., 医学部, 助教授 (90146598)
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| Project Period (FY) |
1997 – 1999
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| Keywords | gene transfer / adenovirus / mutated receptors / TGF-β / CNP / TEPI / D / N Ras / fibrosis |
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| Research Abstract |
1. By adenovirus-mediated gene transfer of a dominant-negative H-ras, p21WAF1, C-type natriuretic peptide (CNP) or tissue factor pathway inhibitor (TFPI), significant inhibition of neointimal formation in injured articles was achieved in rats and rabbits. Using a needle catheter and an adnovirus expressing CNP, inhibition of neointimal hyperplasia can be attained in pig coronary articles.
2. Adenovirus-mediated in vivo TFPI gene transfer into an injured rabbit artery completely inhibits the recurrent thrombosis induced by shear stress even in the presence of catecholamine, without affecting systematic coagulation status. This method may have the potential the treatment of human thrombosis.
3. A truncated TGF-β type II receptor works as a dominant-negative receptor to suppress TGF-βsignaling. Introducing the truncated TGF-β receptor into livers of dimethylnitrosamine-treated rats markedly inhibited liver fibrosis and saved all rats, indicating that TGF-β does play a central role in fibrogenesis and that anti-TGF-β intervention could be therapeutically useful.
4. A soluble TGF-β receptor expressed in muscle effectively suppressed TGF-β signaling in a remote organ, liver as the truncated TGF-β receptor did. This strategy should facilitate clarification of the role of TGF-β (and other growth factors) in vivo in various organs where direct gene transfer seems to be difficult.
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