Enhanced anti-fibrotic activity of plasmid DNA expressing small interference RNA for TGF-beta 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-betaR) 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-betaR 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-betaR over-expression and the collagen content of mice kidney, in marked contrast to free plasmid DNA injection. It is concluded that retrograde injection of TGF-betaR siRNA expression vector plasmid DNA complexed with the cationized gelatin is available to suppress the progression of renal interstitial fibrosis.
Kushibiki
Toshihiro
T
Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Kawara-cho Shogoin, Sakyo-ku, Kyoto, Japan.
Nagata-Nakajima
Natsuki
N
Sugai
Manabu
M
Shimizu
Akira
A
Tabata
Yasuhiko
Y
D000588:Amines; D000818:Animals; D002412:Cations; D004195:Disease Models, Animal; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D005780:Gelatin; D005786:Gene Expression Regulation / Q000502:physiology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D007672:Kidney Cortex / Q000473:pathology* / Q000502:physiology; D007674:Kidney Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000096:biosynthesis / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering / Q000096:biosynthesis / Q000235:genetics*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics*
D000588:Amines; D002412:Cations; D034741:RNA, Small Interfering; D018125:Receptors, Transforming Growth Factor beta; D005780:Gelatin; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II