Nishimura Koyo, Ogawa Koki, Kawaguchi Maho, Fumoto Shintaro, Mukai Hidefumi, Kawakami Shigeru
Department of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, Japan.
Department of Pharmaceutics, Graduate School of Biomedical Sciences, Nagasaki University,1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, Japan.
Pharmaceutics. 2021 Jan 18;13(1):115. doi: 10.3390/pharmaceutics13010115.
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.
基因治疗有望用于治疗腹膜纤维化，这是一个与长期腹膜透析相关的严重问题。肝细胞生长因子（HGF）是一种著名的抗纤维化基因。我们开发了一种超声和纳米气泡介导（声孔效应）的基因转染系统，该系统可选择性地靶向腹膜组织。因此，我们试图通过基于声孔效应的人HGF（hHGF）基因转染来治疗小鼠的腹膜纤维化。为了制备腹膜纤维化模型，给小鼠腹腔注射葡萄糖酸氯己定。我们通过分析以下因素来评估基于声孔效应的hHGF转染的预防和治疗效果：羟脯氨酸水平、腹膜厚度和腹膜平衡试验。还使用多色深度成像评估了声孔效应的转基因表达特征。在小鼠的早期纤维化中，在间皮下层观察到了通过声孔效应的转基因表达。基于声孔效应的hHGF转染对早期腹膜纤维化不仅具有预防作用，还具有治疗作用。就纤维化状态下腹膜中转基因表达的转染特征而言，基于声孔效应的hHGF转染可能适用于腹膜纤维化的治疗。
