| Co-Investigator(Kenkyū-buntansha) |
MIKI Makoto Tohoku Univ Hosp, Assistant Professor, 医学部・附属病院, 助手 (30312656)
EBINA Masahito Tohoku Univ Hosp, Assistant Professor, 医学部・附属病院, 助手 (10280885)
HAGIWARA Koichi Tohoku Univ Hosp, Senior Assistant Professor, 医学部・附属病院, 講師 (00240705)
NAKAMURA Toshikazu Osaka Univ, Professor, 大学院・医学研究科, 教授 (00049397)
NARUMI Koh Tohoku Univ Hosp, Assistant Professor, 医学部・附属病院, 助手 (30302219)
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| Research Abstract |
Hepatocyte growth factor (HGF) is a multi-organ regeneration factor including the anti-apoptotic, angiogenic, proliferative, and morphogenic activity functioning not only in liver but kidney or lung. In the current investigation, in order to apply the HGF gene transfer in the clinical setting for acute lung injury (ALI) and lung fibrosis, we have explored (1) the use of high-expression but antigenic adenoviral vector in the context of administration route, and (2) the use of low-expression but local and non-inflammatory plasmid vector in mouse model. Although high HGF protein was detected by intratracheal Ad-HGF administration, the bleomycin induced ALI and fibrosis persisted with reduced HGF effect. In contrast, in spite of the fact that only fraction of HGF was delivered to the lung by the way of intraperitoneal of intravenous administration of Ad-HGF, the bleomycin induced ALI and fibrosis had been suppressed through repression of both alveolar epithelial cell apoptosis and TGF-b expression. When MAA-PEI was introduced to mix plasmid HGF vector for local HGF expression in the lung, the expression efficiency increased by 10 fold (1 ug plasmid) compared with naked plasmid vector, and the duration of HGF expression prolonged for more than 10 days. Furthemore the concentration of HGF in the lung was only one thousandth of the amount yielded by Ad-HGF, the bleomycin induced ALI and fibrosis was efficiently suppressed. Taken together, while high HGF expression and suppression of lung inflammation was obtained using non-tracheal Ad-HGF administration in the bleomycin induced ALI and fibrosis, local, non-inflammatory and repeatable feature of HGF plasmid/MAA-PEI indicates a possible modality for clinical application in ALI or fibrosis.
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