2007 Fiscal Year Final Research Report Summary
Basic research on gene therapy by pulmonary epithelial cell growth factor on acute and chronic lung injury
| Project/Area Number |
18591987
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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 |
Emergency medicine
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| Research Institution | Yokohama City University |
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Principal Investigator |
KURAHASHI Kiyoyasu Yokohama City University, Graduate School of Medicine, Department of Anesthesiology and Critical Care, Associate professor (50234539)
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| Co-Investigator(Kenkyū-buntansha) |
YAZAWA Takuya Yokohama City University, Department of Applied Pathobiology, Graduate School of Medicine, Associate professor (50251054)
KANEGAE Yumi The university of Tokyo, Laboratory of Molecular Genetics The Institute of Medical Science, Assistant professor (80251453)
YAMADA Yoshitsugu The University of Tokyo, Department of Anesthesiology, Professor (30166748)
BABA Yasuko Yokohama City Univeristy, Department of Anesthesiology and Critical Care, Graduate School of Medicine, Assistant professor (80453041)
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| Project Period (FY) |
2006 – 2007
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| Keywords | gene therapy / adenovirus / acute lung injury / pulmonary fibrosis / sepsis / growth factors / epithelial cell / lung protection |
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| Research Abstract |
We could successfully establish a mouse model of pulmonary fibrosis by continuous subcutaneous administration of bleomycin using osmotic pump. Using this model, we tested therapeutic effects of intra-tracheal KGF expressing adenovirus vector (Ad-KGF) on pulmonary fibrosis. When Ad-KGF was administered to the mice, fibrosis was attenuated and lung function including lung elasticity was improved compared with mice instilled either saline or empty vector (Ad-1W1). As a result, administration of Ad-KGF reduced mortality rate. We tested two different doses, 1.0×10^8PFU (low dose) and 1.0×10^9PFU (high dose). Ad-1W1 caused dose dependent mortality increase, suggesting vector related lung injury. However, high dose of Ad-KGF administration significantly reduced mortality rate as compared with low dose of Ad-KGF, suggesting that higher expression of KGF overcame negative effects of vector administration.
KGF and other growth factors have been tested on animal models by administering prior to the occurrence of pulmonary fibrosis; which are considered to be a therapy for acute lung injury or a prevention of fibrosis, hence were not concluded as "the therapy for fibrosis." We administered Ad-KGF after the occurrence of fibrosis and thus the result of the present study has significance as a treatment of pulmonary fibrosis.
Further investigation such as (1) to study the mechanism of the therapeutic effects of Ad-KGF, (2) to study long term effects and adverse effects of the therapy, and (3) to improve virus vector in terms of reducing inflammation, would warrant the steps to clinical application of this therapy.
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[Journal Article] Keratinocyte Growth Factor Gene Transduction Ameliorates Acute Lung Injury and Mortality in Mice2007
Author(s)
Baba, Y, Yazawa, T, Kanegae, Y, Sakamoto, S, Saito, I, Morimura, N, Goto, T, Yamada, Y, Kurahashi, K
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Journal Title
Human Gene Therapy 18
Pages: 130-41
Description
「研究成果報告書概要(欧文)」より
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