Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, China.
Nanoscale Res Lett. 2012 Aug 9;7(1):451. doi: 10.1186/1556-276X-7-451.
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.
聚乙烯亚胺 (PEI) 是一种阳离子聚合物，是最有效的非病毒基因治疗载体之一。核心蛋白聚糖 (DCN) 是肾小球系膜细胞 (MC) 分泌的富含亮氨酸的蛋白聚糖，是治疗肾小球肾炎的一种很有前途的抗纤维化药物。在这项研究中，我们使用不同 N/P 比值的 PEI-DCN 纳米复合物在体外转染 MC，并通过向左侧肾动脉注射将表达 MC 载体的 PEI-DCN 递送至体内大鼠抗 Thy1.1 肾炎肾组织。在培养的 MC 中，N/P 为 20 的 PEI-质粒 DNA 复合物具有最高的转染效率和最低的细胞毒性。注射后，PEI-DCN 复合物的 MC 载体成功地将外源性基因转移到大鼠抗 Thy1.1 肾炎模型的肾小球中。表达 DCN 的外源性 MC 主要位于系膜和肾小球毛细血管中。在病变肾小球中过表达 DCN 可导致胶原 IV 沉积和 MC 增殖的抑制。注射载体后，大鼠肾炎的病理变化得到缓解。这些发现表明，PEI-DNA 纳米复合物与 MC 载体递送的 DCN 基因是治疗肾小球肾炎的一种很有前途的治疗方法。
