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

Koyo Nishimura,Shigeru Kawakami,Shintaro Fumoto,Maho Kawaguchi,Koki Ogawa,Hidefumi Mukai

doi:10.3390/pharmaceutics13010115

Koyo Nishimura, Shigeru Kawakami + Show 4 more

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https://doi.org/10.3390/pharmaceutics13010115

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Abstract

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.

Highlights

Chronic kidney disease (CKD) patients are increasing worldwide, with over 10% of the world population affected [1], and end-stage CKD patients are expected to increase.Peritoneal dialysis is a replacement therapy for patients with end-stage CKD
To evaluate the preventive effect of human HGF (hHGF) transfection by sonoporation on peritoneal fibrosis, we transfected the hHGF gene by sonoporation followed by 14 days of convective
To evaluate the preventive effect hHGF transfection by sonoporation on peritoneal group was lower than that of only group or ultrasound group

Summary

Introduction

Chronic kidney disease (CKD) patients are increasing worldwide, with over 10% of the world population affected [1], and end-stage CKD patients are expected to increase. Peritoneal dialysis is a replacement therapy for patients with end-stage CKD. Peritoneal dialysis has some advantages over hemodialysis, such as maintenance of kidney function, lifestyle flexibility, and independence. Long-term peritoneal dialysis often causes peritoneal fibrosis, which leads to the interruption of treatment. Glucocorticoids and tamoxifen have been shown to have beneficial effects [2], curative therapy for peritoneal fibrosis has not been developed. To improve the quality of life of peritoneal dialysis patients, the development of prevention and therapeutic strategies for peritoneal fibrosis is essential

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