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TGF-β1-siRNA delivery with nanoparticles inhibits peritoneal fibrosis

Gene Therapy volume 22, pages 333–340 (2015)Cite this article

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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.

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Acknowledgements

We thank Motomu Shimaoka (Professor of Molecular Pathobiology, Mie University School of Medicine) for discussion and comments regarding the manuscript. This work was supported by JSPS KAKENHI (grant number 25461252) and MEXT-Supported Program for Strategic Research Foundations at Private Universities, 2013–2017 (S1211029).

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Authors and Affiliations

  1. Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan

    H Yoshizawa, Y Morishita, M Watanabe, S Muto, E Kusano & D Nagata

  2. Department of Medical Physiology, Meiji Pharmaceutical University, Tokyo, Japan

    K Ishibashi

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  1. H Yoshizawa
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  2. Y Morishita
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  3. M Watanabe
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  4. K Ishibashi
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Correspondence to Y Morishita.

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Yoshizawa, H., Morishita, Y., Watanabe, M. et al. TGF-β1-siRNA delivery with nanoparticles inhibits peritoneal fibrosis. Gene Ther 22, 333–340 (2015). https://doi.org/10.1038/gt.2014.116

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