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: H Yoshizawa, Y Morishita, M Watanabe, K Ishibashi, S Muto, E Kusano, D Nagata
• Journal: Gene therapy (Gene Ther) Vol. 22 Issue 4 Pg. 333-40 (Apr 2015) ISSN: 1476-5462 [Electronic] England
• PMID: 25567535 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Small Interfering
• Transforming Growth Factor beta1

Topics

• Animals
• Disease Models, Animal
• Male
• Mice, Inbred C57BL
• Myofibroblasts (metabolism)
• Nanoparticles (therapeutic use)
• Peritoneal Fibrosis (therapy)
• RNA, Small Interfering (metabolism, therapeutic use)
• Transforming Growth Factor beta1 (metabolism)