R. S. Mehta Jain Department of Biochemistry and Cell Biology, Vision Research Foundation, Chennai, India ; Birla Institute of Technology and Science, Pilani (Rajasthan), India.
PLoS One. 2013 Sep 9;8(9):e71982. doi: 10.1371/journal.pone.0071982. eCollection 2013.
Increased levels of intracellular copper stimulate angiogenesis in human umbilical vein endothelial cells (HUVECs). Copper transporter 1 (CTR1) is a copper importer present in the cell membrane and plays a major role in copper transport. In this study, three siRNAs targeting CTR1 mRNA were designed and screened for gene silencing. HUVECs when exposed to 100 µM copper showed 3 fold increased proliferation, migration by 1.8-fold and tube formation by 1.8-fold. One of the designed CTR1 siRNA (si 1) at 10 nM concentration decreased proliferation by 2.5-fold, migration by 4-fold and tube formation by 2.8-fold. Rabbit corneal packet assay also showed considerable decrease in matrigel induced blood vessel formation by si 1 when compared to untreated control. The designed si 1 when topically applied inhibited angiogenesis. This can be further developed for therapeutic application.
细胞内铜水平升高可刺激人脐静脉内皮细胞（HUVEC）血管生成。铜转运蛋白 1（CTR1）是一种存在于细胞膜上的铜转运体，在铜转运中起主要作用。在这项研究中，设计并筛选了三种针对 CTR1 mRNA 的 siRNA 进行基因沉默。当 HUVEC 暴露于 100µM 铜时，增殖增加了 3 倍，迁移增加了 1.8 倍，管形成增加了 1.8 倍。在 10 nM 浓度下，设计的 CTR1 siRNA（si1）使增殖减少了 2.5 倍，迁移增加了 4 倍，管形成增加了 2.8 倍。兔角膜包被实验也表明，与未处理的对照组相比，si1 可显著减少基质胶诱导的血管生成。设计的 si1 局部应用可抑制血管生成。这可以进一步开发用于治疗应用。
