Suppression of Peritoneal Fibrosis by Sonoporation of Hepatocyte Growth Factor Gene-Encoding Plasmid DNA in Mice

被引:13
作者
Nishimura, Koyo [1 ]
Ogawa, Koki [1 ]
Kawaguchi, Maho [1 ]
Fumoto, Shintaro [2 ]
Mukai, Hidefumi [1 ,3 ]
Kawakami, Shigeru [1 ]
机构
[1] Nagasaki Univ, Grad Sch Biomed Sci, Dept Pharmaceut Informat, 1-7-1 Sakamoto, Nagasaki, Nagasaki 8528588, Japan
[2] Nagasaki Univ, Grad Sch Biomed Sci, Dept Pharmaceut, 1-7-1 Sakamoto, Nagasaki, Nagasaki 8528588, Japan
[3] RIKEN Ctr Biosyst Dynam Res, Lab Mol Delivery & Imaging Technol, Chuo Ku, 6-7-3 Minatojima Minamimachi, Kobe, Hyogo 6500047, Japan
关键词
nanobubbles; ultrasound; gene therapy; peritoneal fibrosis; multicolor deep imaging; hepatocyte growth factor;
D O I
10.3390/pharmaceutics13010115
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Gene therapy is expected to be used for the treatment of peritoneal fibrosis, which is a serious problem associated with long-term peritoneal dialysis. Hepatocyte growth factor (HGF) is a well-known anti-fibrotic gene. We developed an ultrasound and nanobubble-mediated (sonoporation) gene transfection system, which selectively targets peritoneal tissues. Thus, we attempted to treat peritoneal fibrosis by sonoporation-based human HGF (hHGF) gene transfection in mice. To prepare a model of peritoneal fibrosis, mice were intraperitoneally injected with chlorhexidine digluconate. We evaluated the preventive and curative effects of sonoporation-based hHGF transfection by analyzing the following factors: hydroxyproline level, peritoneum thickness, and the peritoneal equilibration test. The transgene expression characteristics of sonoporation were also evaluated using multicolor deep imaging. In early-stage fibrosis in mice, transgene expression by sonoporation was observed in the submesothelial layer. Sonoporation-based hHGF transfection showed not only a preventive effect but also a curative effect for early-stage peritoneal fibrosis. Sonoporation-based hHGF transfection may be suitable for the treatment of peritoneal fibrosis regarding the transfection characteristics of transgene expression in the peritoneum under fibrosis.
引用
收藏
页码:1 / 14
页数:14
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