Enhanced anti-fibrotic activity of plasmid DNA expressing small interference RNA for TGF-β type II receptor for a mouse model of obstructive nephropathy by cationized gelatin prepared from different amine compounds

The objective of this study is to increase the transfection efficiency of a plasmid DNA expressing small interference RNA (siRNA) for transforming growth factor-beta receptor (TGF-beta R) by various cationized gelatins of non-viral carrier and evaluate the anti-fibrotic effect with a mouse model of unilateral ureteral obstruction (UUO). Ethylenediamine, putrescine, spermidine or spermine was chemically introduced to the carboxyl groups of gelatin for the cationization. The plasmid DNA of TGF-beta R siRNA expression vector with or without complexation of each cationized gelatin was injected to the left kidney of mice via the ureter to prevent the progression of renal fibrosis of UUO mice. Irrespective of the type of cationized. gelatin, the injection of plasmid DNA-cationized gelatin complex significantly decreased the renal level of TGF-beta R overexpression and the collagen content of mice kidney, in marked contrast to free plasmid DNA injection. It is concluded that retrograde injection of TGF-beta R siRNA expression vector plasmid DNA complexed with the cationized gelatin is available to suppress the progression of renal interstitial fibrosis. (C) 2005 Elsevier B.V. All rights reserved.