title: Effects of Fibrotic Tissue on Liver-targeted Hydrodynamic Gene Delivery.
abstract: Hydrodynamic gene delivery is a common method for gene transfer to the liver of small animals, and its clinical applicability in large animals has been demonstrated. Previous studies focused on functional analyses of therapeutic genes in animals with normal livers and little, however, is known regarding its effectiveness and safety in animals with liver fibrosis. Therefore, this study aimed to examine the effects of liver fibrosis on hydrodynamic gene delivery efficiency using a rat liver fibrosis model. We demonstrated for the first time, using pCMV-Luc plasmid, that this procedure is safe and that the amount of fibrotic tissue in the liver decreases gene delivery efficiency, resulting in decrease in luciferase activity depending on the volume of fibrotic tissue in the liver and the number of hepatocytes that are immunohistochemically stained positive for transgene product. We further demonstrate that antifibrotic gene therapy with matrix metalloproteinase-13 gene reduces liver fibrosis and improves efficiency of hydrodynamic gene delivery. These results demonstrate the negative effects of fibrotic tissue on hydrodynamic gene delivery and its recovery by appropriate antifibrotic therapy.
authors: Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan.
authors: Yuji
authors: Y
authors: Kobayashi
authors: Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan.
authors: Kenya
authors: K
authors: Kamimura
authors: Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan.
authors: Hiroyuki
authors: H
authors: Abe
authors: Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan.
authors: Takeshi
authors: T
authors: Yokoo
authors: Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan.
authors: Kohei
authors: K
authors: Ogawa
authors: Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan.
authors: Yoko
authors: Y
authors: Shinagawa-Kobayashi
authors: Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan.
authors: Ryo
authors: R
authors: Goto
authors: Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan.
authors: Ryosuke
authors: R
authors: Inoue
authors: Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, School of Medicine, Tokai University, Isehara, Kanagawa, Japan.|The Institute of Medical Sciences, Tokai University, Isehara, Kanagawa Japan.
authors: Masato
authors: M
authors: Ohtsuka
authors: Department of Regenerative Medicine, Basic Medical Science, School of Medicine, Tokai University, Isehara, Kanagawa, Japan.
authors: Hiromi
authors: H
authors: Miura
authors: Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan.
authors: Tsutomu
authors: T
authors: Kanefuji
authors: Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan.
authors: Takeshi
authors: T
authors: Suda
authors: Division of Thoracic and Cardiovascular Surgery, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan.
authors: Masanori
authors: M
authors: Tsuchida
authors: Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan.
authors: Yutaka
authors: Y
authors: Aoyagi
authors: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia, USA.
authors: Guisheng
authors: G
authors: Zhang
authors: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia, USA.
authors: Dexi
authors: D
authors: Liu
authors: Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan.
authors: Shuji
authors: S
authors: Terai