Delivery of microRNA-146a with polyethylenimine nanoparticles inhibits renal fibrosis in vivo

Yoshiyuki Morishita,1 Toshimi Imai,1 Hiromichi Yoshizawa,1 Minami Watanabe,1 Kenichi Ishibashi,2 Shigeaki Muto,1 Daisuke Nagata1 1Division of Nephrology, Department of Medicine, Jichi Medical University, Tochigi, 2Department of Medical Physiology, Meiji Pharmaceutical University, Tokyo, Japan Abst...

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Autores principales:	Morishita Y, Imai T, Yoshizawa H, Watanabe M, Ishibashi K, Muto S, Nagata D
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/3fd186b2bcca417fb42fe072985b1f35
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spelling	oai:doaj.org-article:3fd186b2bcca417fb42fe072985b1f352021-12-02T02:56:02ZDelivery of microRNA-146a with polyethylenimine nanoparticles inhibits renal fibrosis in vivo1178-2013https://doaj.org/article/3fd186b2bcca417fb42fe072985b1f352015-05-01T00:00:00Zhttp://www.dovepress.com/delivery-of-microrna-146a-with-polyethylenimine-nanoparticles-inhibits-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yoshiyuki Morishita,1 Toshimi Imai,1 Hiromichi Yoshizawa,1 Minami Watanabe,1 Kenichi Ishibashi,2 Shigeaki Muto,1 Daisuke Nagata1 1Division of Nephrology, Department of Medicine, Jichi Medical University, Tochigi, 2Department of Medical Physiology, Meiji Pharmaceutical University, Tokyo, Japan Abstract: Renal fibrosis is the final common pathway leading to end-stage renal disease. Although microRNA (miR) was recently shown to be involved in the development of renal fibrosis, few studies have focused on the effects on renal fibrosis of exogenous miR delivered in an in vivo therapeutic setting. The study reported here investigated the effects of miR-146a delivery using polyethylenimine nanoparticles (PEI-NPs) on renal fibrosis in vivo. PEI-NPs bearing miR-146 or control-miR (nitrogen/phosphate ratio: 6) were injected into the tail vein of a mouse model of renal fibrosis induced by unilateral ureteral obstruction. PEI-NPs bearing miR-146 significantly enhanced miR-146a expression in the obstructed kidney compared with the control group, while inhibiting the renal fibrosis area, expression of alpha-smooth muscle actin, and infiltration of F4/80-positive macrophages into the obstructed kidney. In addition, PEI-NPs bearing miR-146a inhibited the transforming growth factor beta 1–Smad and tumor necrosis factor receptor-associated factor 6–nuclear factor kappa B signaling pathways. Control-miR-PEI-NPs did not show any of these effects. These results suggest that the delivery of miR-146a attenuated renal fibrosis by inhibiting pro-fibrotic and inflammatory signaling pathways and that the delivery of appropriate miRs may be a therapeutic option for preventing renal fibrosis in vivo. Keywords: miR, end-stage renal disease, pro-fibrotic signaling pathway, inflammatory signaling pathwayMorishita YImai TYoshizawa HWatanabe MIshibashi KMuto SNagata DDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 3475-3488 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Morishita Y Imai T Yoshizawa H Watanabe M Ishibashi K Muto S Nagata D Delivery of microRNA-146a with polyethylenimine nanoparticles inhibits renal fibrosis in vivo
description	Yoshiyuki Morishita,1 Toshimi Imai,1 Hiromichi Yoshizawa,1 Minami Watanabe,1 Kenichi Ishibashi,2 Shigeaki Muto,1 Daisuke Nagata1 1Division of Nephrology, Department of Medicine, Jichi Medical University, Tochigi, 2Department of Medical Physiology, Meiji Pharmaceutical University, Tokyo, Japan Abstract: Renal fibrosis is the final common pathway leading to end-stage renal disease. Although microRNA (miR) was recently shown to be involved in the development of renal fibrosis, few studies have focused on the effects on renal fibrosis of exogenous miR delivered in an in vivo therapeutic setting. The study reported here investigated the effects of miR-146a delivery using polyethylenimine nanoparticles (PEI-NPs) on renal fibrosis in vivo. PEI-NPs bearing miR-146 or control-miR (nitrogen/phosphate ratio: 6) were injected into the tail vein of a mouse model of renal fibrosis induced by unilateral ureteral obstruction. PEI-NPs bearing miR-146 significantly enhanced miR-146a expression in the obstructed kidney compared with the control group, while inhibiting the renal fibrosis area, expression of alpha-smooth muscle actin, and infiltration of F4/80-positive macrophages into the obstructed kidney. In addition, PEI-NPs bearing miR-146a inhibited the transforming growth factor beta 1–Smad and tumor necrosis factor receptor-associated factor 6–nuclear factor kappa B signaling pathways. Control-miR-PEI-NPs did not show any of these effects. These results suggest that the delivery of miR-146a attenuated renal fibrosis by inhibiting pro-fibrotic and inflammatory signaling pathways and that the delivery of appropriate miRs may be a therapeutic option for preventing renal fibrosis in vivo. Keywords: miR, end-stage renal disease, pro-fibrotic signaling pathway, inflammatory signaling pathway
format	article
author	Morishita Y Imai T Yoshizawa H Watanabe M Ishibashi K Muto S Nagata D
author_facet	Morishita Y Imai T Yoshizawa H Watanabe M Ishibashi K Muto S Nagata D
author_sort	Morishita Y
title	Delivery of microRNA-146a with polyethylenimine nanoparticles inhibits renal fibrosis in vivo
title_short	Delivery of microRNA-146a with polyethylenimine nanoparticles inhibits renal fibrosis in vivo
title_full	Delivery of microRNA-146a with polyethylenimine nanoparticles inhibits renal fibrosis in vivo
title_fullStr	Delivery of microRNA-146a with polyethylenimine nanoparticles inhibits renal fibrosis in vivo
title_full_unstemmed	Delivery of microRNA-146a with polyethylenimine nanoparticles inhibits renal fibrosis in vivo
title_sort	delivery of microrna-146a with polyethylenimine nanoparticles inhibits renal fibrosis in vivo
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/3fd186b2bcca417fb42fe072985b1f35
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Delivery of microRNA-146a with polyethylenimine nanoparticles inhibits renal fibrosis in vivo

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