Nano-sized carriers in gene therapy for peritoneal fibrosis in vivo

Figures & data

Figure 1. Mechanism of peritoneal fibrosis development.

TGF: transforming growth factor; TNF: tumor necrosis factor; IL: interleukin; SMA: smooth muscle actin.

Table 1. Gene therapies and nano-sized carriers for the treatment of peritoneal fibrosis.

Vector		Transgene	Administration route	Effects	Authors (published year)	Reference No.
Virus vectors	Adenovirus	Angiostatin-DNA	Intraperitoneal injection	Ameliorated peritoneal fibrosis by inhibiting angiogenesis	Hoff and Margetts (2006)	[34]
	Adenovirus	Angiostatin-DNA	Intraperitoneal injection	Ameliorated peritoneal fibrosis by inhibiting angiogenesis	Margetts et al. (2002)	[35]
	Adenovirus	Decorin-DNA	Intraperitoneal injection	Inhibited collagen accumulation in peritoneum without improving ultrafiltration ability	Margetts et al. (2002)	[35]
	Adenovirus	BMP-7-DNA	Intraperitoneal injection	Ameliorated peritoneal fibrosis	Yu et al. (2009)	[36]
	AAV	Decorin-DNA	Intraperitoneal injection	Inhibited peritoneal fibrosis with preservation of peritoneal cell size, decreased peritoneal thickness, and decreased expression of α-SMA	Chaudhary et al. (2014)	[37]
	Retrovirus	CTGF-siRNA	Applied to cultured human peritoneal mesothelial cells	Inhibited production of the extracellular matrix such as fibronectin, collagen I and laminin and VEGF expression under stimulation of TGF-β1	Xiao et al. (2010)	[38]
Non-viral vectors	Liposome nanoparticles	TGF-β1-siRNA	Intraperitoneal injection	Inhibited TGF-β1 expression in peritoneum, and inhibited peritoneal fibrosis with decreased proliferation of α-SMA-positive myofibroblasts	Yoshizawa et al. (2015)	[39]
	Gold nanoparticles	Decorin-DNA	Intraperitoneal injection	Inhibited peritoneal fibrosis	Chaudhary et al. (2014)	[37]
	Cationic gelatin nanoparticles	HSP47-siRNA	Intraperitoneal injection	Inhibited expression of HSP47 on peritoneum, and inhibited peritoneal fibrosis with decreased expression of type III collagen, TGF-β1, α-SMA, and MCP-1	Obata et al. (2012)	[40]
Naked, artificial, modified oligonucleotides	None	HSP47-antisense oligonucleotides	Intraperitoneal injection	Inhibited expression of HSP47, and inhibited peritoneal fibrosis with decreased expression of types Ⅰ and Ⅲ collagen and α-SMA, and inhibited macrophage infiltration	Nishino et al. (2003)	[41]
	None	MicroRNA-21-5p-inhibitor-BNA	Intraperitoneal injection	Inhibited peritoneal fibrosis with increased expression of PPAR-α	Morishita et al. (2016)	[42]
Ultrasound-microbubble-mediated transfer	None	Smad7-plasmid DNA	Intraperitoneal injection	Inhibited peritoneal fibrosis	Guo et al. (2007)	[43]
	None	MicroRNA-30a	Intraperitoneal injection	Inhibited peritoneal fibrosis with inhibition of Snail signaling pathway	Zhou et al. (2013)	[44]
	None	MicroRNA-29b	Intraperitoneal injection	Inhibited peritoneal fibrosis with inhibition of TGF-β1 signaling pathway	Yu et al. (2014)	[45]

BMP-7: bone morphogenic protein-7; AAV: adeno-associated viral vector; α-SMA: α-smooth muscle actin; CTGF: connective tissue growth factor; VEGF: vascular endothelial growth factor; IκB-α: I-kappa-B-alpha; TGF-β₁: transforming growth factor-β₁; HSP47: heat shock protein 47; MCP-1: monocyte chemoattractant protein-1; PPAR-α: peroxisome proliferator-activated receptor; Smad7; mothers against decapentaplegic homolog 7.

Figure 2. Viral and non-viral vectors for renal fibrosis in vivo.

Hoff CM, Margetts PJ. Adenovirus-based transient expression systems for peritoneal membrane research. Perit Dial Int. 2006;26:547–558. Epub 2006 Sep 16.

 Web of Science ®Google Scholar

Margetts PJ, Gyorffy S, Kolb M, et al. Antiangiogenic and antifibrotic gene therapy in a chronic infusion model of peritoneal dialysis in rats. J Am Soc Nephrol. 2002;13:721–728. Epub 2002 Feb 22.

 PubMed Web of Science ®Google Scholar

Yu M-A, Shin K-S, Kim JH, et al. HGF and BMP-7 ameliorate high glucose-induced epithelial-to-mesenchymal transition of peritoneal mesothelium. J Am Soc Nephrol. 2009;20:567–581. Epub 2009 Feb 6.

 PubMed Web of Science ®Google Scholar

Chaudhary K, Moore H, Tandon A, et al. Nanotechnology and adeno-associated virus-based decorin gene therapy ameliorates peritoneal fibrosis. Am J Physiol Renal Physiol. 2014;307:F777–F782. Epub 2014 Jul 25.

 Web of Science ®Google Scholar

Xiao L, Sun L, Liu F-Y, et al. Connective tissue growth factor knockdown attenuated matrix protein production and vascular endothelial growth factor expression induced by transforming growth factor-beta1 in cultured human peritoneal mesothelial cells. Ther Apher Dial. 2010;14:27–34. Epub 2010 May 5.

 Web of Science ®Google Scholar

Yoshizawa H, Morishita Y, Watanabe M, et al. TGF-β1-siRNA delivery with nanoparticles inhibits peritoneal fibrosis. Gene Ther. 2015;22:333–340. Epub 2015 Jan 9.

 PubMed Web of Science ®Google Scholar

Obata Y, Nishino T, Kushibiki T, et al. HSP47 siRNA conjugated with cationized gelatin microspheres suppresses peritoneal fibrosis in mice. Acta Biomater. 2012;8:2688–2696. Epub 2012 Apr 11.

 PubMed Web of Science ®Google Scholar

Nishino T, Miyazaki M, Abe K, et al. Antisense oligonucleotides against collagen-binding stress protein HSP47 suppress peritoneal fibrosis in rats. Kidney Int. 2003;64:887–896. Epub 2003 Aug 13.

 PubMed Web of Science ®Google Scholar

Morishita Y, Yoshizawa H, Watanabe M, et al. MicroRNA expression profiling in peritoneal fibrosis. Transl Res. 2016;169:47–66. Epub 2015 Dec 1.

 Web of Science ®Google Scholar

Guo H, Leung JC, Chan LY, et al. Ultrasound-contrast agent mediated naked gene delivery in the peritoneal cavity of adult rat. Gene Ther. 2007;14:1712–1720. Epub 2007 Oct 26.

 PubMed Web of Science ®Google Scholar

Zhou Q, Yang M, Lan H, et al. miR-30a negatively regulates TGF-β1-induced epithelial-mesenchymal transition and peritoneal fibrosis by targeting Snai1. Am J Pathol. 2013;183:808–819. Epub 2013 Jul 9.

 PubMed Web of Science ®Google Scholar

Yu J-W, Duan W-J, Huang X-R, et al. MicroRNA-29b inhibits peritoneal fibrosis in a mouse model of peritoneal dialysis. Lab Invest. 2014;94:978–990. Epub 2014 Jul 22.

 Web of Science ®Google Scholar