1996 Fiscal Year Final Research Report Summary
Evaluation of expression of multiorganotrophic factor HGF using adenovirus vector containing rat HGF gene and its repressive effects on bleomycin induced lung injury and fibrosis in mice
| Project/Area Number |
07807061
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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 |
Respiratory organ internal medicine
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| Research Institution | Tohoku University |
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Principal Investigator |
YAEKASHIWA Masahiro Institute of Development, Aging and Cancer, Tohoku University, Assistant Professor, 加齢医学研究所, 助手 (70261477)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Toshikazu Division of Biochemistry, Biomedical Research Center, Osaka University Medical S, 医学部, 教授 (00049397)
SAIJIYO Yasuo Institute of Development, Aging and Cancer, Tohoku University, Assistant Profess, 加齢医学研究所, 助手 (10270828)
NUKIWA Toshihiro Institute of Development, Aging and Cancer, Tohoku University, Professor, 加齢医学研究所, 教授 (40129036)
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| Project Period (FY) |
1995 – 1996
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| Keywords | HGF / Adenovirus vector / Bleomycin / Lung Injury / Lung Fibrosis / Lung Epithelium |
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| Research Abstract |
Although animal experiments revealed that recombinant hepatocyte growth factor (HGF) repressed lung injury and fibrosis caused by bleomycin (BLM), practical application requires methods for long term continuous administration. One way to achieve continuous administration is to utilize HGF produced by transfected HGF gene. Adenovirus vector (Adex1CAHHGF : constructed with rat HGF gene under control of CAG promoter) was investigated in its therapeutic effects in mice. BLM (100mg/kg) was administrated into C57BL/6 mice for 7 days as a constant s.c.infusion by an minipump to induce lung injury. Adex1CAHHGF (6x10<@D18@>D1 pfu) was transduced into mice intraperitoneally at day 0. In Adex1CAHHGR transduced mice (group I), HGF concentration in lung elevated at day 7, and was significantly higher (888(]SY.+-。[)401 ng/g tissue, n=3) than in control mice (group II) (400.9(]YS.+-.[)88.5, n=4) at day 28. HGF in liver elevated after day 3, and was 2 fold higher in group I than in II at day 28. In group I,fibrotic changes were apparently repressed and showed less focal lesions in subpleural area than in group II.Numerical fibrotic score in group I was significantly smaller than that in group II (1.8(]SY.+-。[)0.2 vs.2.7(]SY.+-。[)0.2, p<0.05n=3,4, respectively). Thus, HGF produced by adenoviral transgene was shown to be feasible one step to control lung injury in animal model.
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Research Products
(12 results)
