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
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
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DOI：
10.1016/j.jconrel.2005.11.007
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发表时间：
2006-02-21
影响因子：
10.8
通讯作者：
Tabata, Y
中科院分区：
文献类型：
--
作者：
Kushibiki, T;Nagata-Nakajima, N;Tabata, Y
本研究的目的是提高表达转化生长因子-β受体（TGF-β R）小干扰RNA（siRNA）的质粒DNA在不同阳离子明胶非病毒载体中的转染效率，并在单侧输尿管梗阻（UUO）小鼠模型上评价其抗纤维化作用。采用化学方法将乙二胺、腐胺、亚精胺或精胺引入到明胶的羧基上进行阳离子化。将TGF-β R siRNA表达载体的质粒DNA与或不与每种阳离子化明胶复合，通过输尿管注射到小鼠的左肾，以防止UUO小鼠肾纤维化的进展。不管阳离子化的类型。注射质粒DNA-阳离子明胶复合物可显著降低小鼠肾脏TGF-β R过表达水平和胶原含量，与注射游离质粒DNA形成显著对比。结论：逆行注射TGF-β R siRNA表达载体质粒DNA与阳离子明胶复合物可抑制肾间质纤维化的进展。(C)2005 Elsevier B. V.保留所有权利。
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.