Extracellular glycosaminoglycans modify cellular trafficking of lipoplexes and polyplexes
Extracellular glycosaminoglycans modify cellular trafficking of lipoplexes and polyplexes
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DOI：
10.1074/jbc.m011553200
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发表时间：
2001-09-07
影响因子：
4.8
通讯作者：
Urtti, A
中科院分区：
文献类型：
--
作者：
Ruponen, M;Rönkkö, S;Urtti, A
研究表明，细胞外糖胺聚糖 (GAG) 通过阳离子脂质和聚合物限制基因转移。本研究的目的是阐明与阴离子 GAGS（透明质酸和硫酸乙酰肝素）的相互作用如何改变脂质复合物和聚合复合物的细胞摄取和分布。细胞 DNA 摄取和 GFP 报告基因表达的实验表明，基因表达下降很少能用细胞摄取降低来解释。在大多数情况下，细胞摄取不会因 GAG 与脂质复合物或多聚复合物的结合而改变。硫酸乙酰肝素会降低或阻断报告基因的表达，但透明质酸会增加报告基因的表达；这表明细胞内因素参与其中。共聚焦显微镜实验表明，细胞外硫酸乙酰肝素和透明质酸均被游离载体和 DNA 相关载体带入细胞中。我们得出结论，细胞外 GAG 可能会改变 DNA 复合物的细胞摄取和细胞内行为。
It has been shown that extracellular glycosaminoglycans (GAGs) limit the gene transfer by cationic lipids and polymers. The purpose of this study was to clarify how interactions with anionic GAGS (hyaluronic acid and heparan sulfate) modify the cellular uptake and distribution of lipoplexes and polyplexes. Experiments on cellular DNA uptake and GFP reporter gene expression showed that decreased gene expression can rarely be explained by lower cellular uptake. In most cases, the cellular uptake is not changed by GAG binding to the lipoplexes or polyplexes. Reporter gene expression is decreased or blocked by heparan sulfate, but it is increased by hyaluronic acid; this suggests that intracellular factors are involved. Confocal microscopy experiments demonstrated that extracellular heparan sulfate and hyaluronic acid are taken into cells both with free and DNA-associated carriers. We conclude that extracellular GAGs may alter both the cellular uptake and the intracellular behavior of the DNA complexes.