Suppression of Peritoneal Fibrosis by Sonoporation of Hepatocyte Growth Factor Gene-Encoding Plasmid DNA in Mice
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 transfecti...
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MDPI AG
2021-01-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/1/115 |
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| author | Koyo Nishimura Koki Ogawa Maho Kawaguchi Shintaro Fumoto Hidefumi Mukai Shigeru Kawakami |
| author_facet | Koyo Nishimura Koki Ogawa Maho Kawaguchi Shintaro Fumoto Hidefumi Mukai Shigeru Kawakami |
| author_sort | Koyo Nishimura |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T04:29:36Z |
| format | Article |
| id | doaj.art-3bf888a3d7e8454289d82a4813d57a45 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T04:29:36Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-3bf888a3d7e8454289d82a4813d57a452023-12-03T13:37:03ZengMDPI AGPharmaceutics1999-49232021-01-0113111510.3390/pharmaceutics13010115Suppression of Peritoneal Fibrosis by Sonoporation of Hepatocyte Growth Factor Gene-Encoding Plasmid DNA in MiceKoyo Nishimura0Koki Ogawa1Maho Kawaguchi2Shintaro Fumoto3Hidefumi Mukai4Shigeru Kawakami5Department of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, JapanDepartment of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, JapanDepartment of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, JapanDepartment of Pharmaceutics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, JapanDepartment of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, JapanDepartment of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, JapanGene 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.https://www.mdpi.com/1999-4923/13/1/115nanobubblesultrasoundgene therapyperitoneal fibrosismulticolor deep imaginghepatocyte growth factor |
| spellingShingle | Koyo Nishimura Koki Ogawa Maho Kawaguchi Shintaro Fumoto Hidefumi Mukai Shigeru Kawakami Suppression of Peritoneal Fibrosis by Sonoporation of Hepatocyte Growth Factor Gene-Encoding Plasmid DNA in Mice Pharmaceutics nanobubbles ultrasound gene therapy peritoneal fibrosis multicolor deep imaging hepatocyte growth factor |
| title | Suppression of Peritoneal Fibrosis by Sonoporation of Hepatocyte Growth Factor Gene-Encoding Plasmid DNA in Mice |
| title_full | Suppression of Peritoneal Fibrosis by Sonoporation of Hepatocyte Growth Factor Gene-Encoding Plasmid DNA in Mice |
| title_fullStr | Suppression of Peritoneal Fibrosis by Sonoporation of Hepatocyte Growth Factor Gene-Encoding Plasmid DNA in Mice |
| title_full_unstemmed | Suppression of Peritoneal Fibrosis by Sonoporation of Hepatocyte Growth Factor Gene-Encoding Plasmid DNA in Mice |
| title_short | Suppression of Peritoneal Fibrosis by Sonoporation of Hepatocyte Growth Factor Gene-Encoding Plasmid DNA in Mice |
| title_sort | suppression of peritoneal fibrosis by sonoporation of hepatocyte growth factor gene encoding plasmid dna in mice |
| topic | nanobubbles ultrasound gene therapy peritoneal fibrosis multicolor deep imaging hepatocyte growth factor |
| url | https://www.mdpi.com/1999-4923/13/1/115 |
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