title: TGF-β₁-siRNA delivery with nanoparticles inhibits peritoneal fibrosis.
abstract: Gene therapies may be promising for the treatment of peritoneal fibrosis (PF) in subjects undergoing peritoneal dialysis (PD). However, a method of delivery of treatment genes to the peritoneum is lacking. We attempted to develop an in vivo small interfering RNA (siRNA) delivery system with liposome-based nanoparticles (NPs) to the peritoneum to inhibit PF. Transforming growth factor (TGF)-β1-siRNAs encapsulated in NPs (TGF-β1-siRNAs-NPs) dissolved in PD fluid were injected into the peritoneum of mice with PF three times a week for 2 weeks. TGF-β1-siRNAs-NPs knocked down TGF-β1 expression significantly in the peritoneum and inhibited peritoneal thickening with fibrous changes. TGF-β1-siRNAs-NPs also inhibited the increase of expression of α-smooth muscle actin-positive myofibroblasts. These results suggest that the TGF-β1-siRNA delivery system with NPs described here could be an effective therapeutic option for PF in subjects undergoing PD.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yoshizawa
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Morishita
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Medical Physiology, Meiji Pharmaceutical University, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ishibashi
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Muto
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Kusano
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Nagata
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D008810:Mice, Inbred C57BL; D058628:Myofibroblasts / Q000378:metabolism; D053758:Nanoparticles / Q000627:therapeutic use*; D056627:Peritoneal Fibrosis / Q000628:therapy*; D034741:RNA, Small Interfering / Q000378:metabolism* / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1