1996 Fiscal Year Final Research Report Summary
In vivo roles of growth factors in inflammatory fibroproliferative arterial diseases. -Molecular assessment by in vivo gene transfer into arteries-
| Project/Area Number |
07457172
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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, Faculty of Med., Assis.Prof., 医学部, 講師 (50260378)
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| Co-Investigator(Kenkyū-buntansha) |
SUEISHI Katsuo Kyushu Univ., Faculty of Med., Prof., 医学部, 教授 (70108710)
SETOGUCHI Yasuhiro Juntendo Univ., Faculty of Med., Assis.Prof., 医学部, 助手 (90206649)
TSUTSUI Hiroyuki Kyushu Univ., Faculty of Med., Assis.Prof., 医学部, 講師 (70264017)
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| Project Period (FY) |
1995 – 1996
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| Keywords | recombinant adenovirus / gene transfer / gene therapy / restenosis / atherosclerosis / angiogenesis / TGF-b / H-ras |
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| Research Abstract |
1. We quantitatively evaluated gene expression following adenovirus-mediated gene transfer into balloon-injured canine femoral arteries. High level expression peaked 7 days after transfer retained for a month. Repeat administration was effective to induce gene expression to some extent. Gene expression was also detected in pre-immuned animals, however, the levels correlated inversely to the titer of neutralizing antibodies in serum.
2. Neointimal formation in rat balloon-injured carotid arteries was significantly suppressed by the administration of adenoviruses expressing either a dominat-negative H-Ras, cyclin-dependent kinase inhibitor-p21^<WAF1/Sdi1> or wild-type p53.
3. We succeeded to induce gene expression in canine myocardium using a needle catheter.
4. Adenovirus-mediated transfer of a truncated TGF-b type II receptor inhibited all signaling by TGF-b, suggesting that heteromeric complex formation between the type I and type II receptors is required for all signaling by TGF-b.
5. We analyzed the role of H-Ras and Rac in signaling by TGF-b.
6. We constructed adenoviruses expressing either vascular endothelial growth factor or fibroblast growth factor (FGF) tagged with signal peptide derived from FGF-4. These vectors induced in vivo angiogenesis.
We invented a method to improve adenovirus-mediated gene transfer and expression in vivo.
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[Publications] Kitamura Y., Kitamura T., Sakaue H., Maeda T., Ueno H., Nishio, S.Ohno, S.Osada, M.Sakaue, W.Ogawa, M.Kasuga.: "Interaction of Nck-associated protein 1 with activated GTP-binding protein Rac." Biochem J. 332. 873-878 (1997)
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