Open Access Nano Express

Transgene therapy for rat anti-Thy1.1 glomerulonephritis via mesangial cell vector with a polyethylenimine/decorin nanocomplex

Jian-Yong Sun1, Yu Sun1, Hui-Juan Wu12, Hong-Xia Zhang1, Zhong-Hua Zhao1, Qi Chen1 and Zhi-Gang Zhang12*

Author Affiliations

1 Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China

2 Key Laboratory of Molecular Medicine, Ministry of Education of China, Shanghai Medical College, Fudan University, Shanghai, China

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Nanoscale Research Letters 2012, 7:451  doi:10.1186/1556-276X-7-451

Published: 9 August 2012

Abstract

Polyethylenimine (PEI), a cationic polymer, is one of the most efficient non-viral vectors for transgene therapy. Decorin (DCN), a leucine-rich proteoglycan secreted by glomerular mesangial cells (MC), is a promising anti-fibrotic agent for the treatment of glomerulonephritis. In this study, we used PEI–DCN nanocomplexes with different N/P ratios to transfect MC in vitro and deliver the MC vector with PEI–DCN expressing into rat anti-Thy1.1 nephritis kidney tissue via injection into the left renal artery in vivo. The PEI–plasmid DNA complex at N/P 20 had the highest level of transfection efficiency and the lowest level of cytotoxicity in cultured MC. Following injection, the ex vivo gene was transferred successfully into the glomeruli of the rat anti-Thy1.1 nephritis model by the MC vector with the PEI–DCN complex. The exogenous MC with DCN expression was located mainly in the mesangium and the glomerular capillary. Over-expression of DCN in diseased glomeruli could result in the inhibition of collagen IV deposition and MC proliferation. The pathological changes of rat nephritis were alleviated following injection of the vector. These findings demonstrate that the DCN gene delivered by the PEI–DNA nanocomplex with the MC vector is a promising therapeutic method for the treatment of glomerulonephritis.

Keywords:
Polyethylenimine; Decorin; Nanocomplex; Mesangial cell; Rat anti-Thy1.1 nephritis