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Published on: March 30, 2019
CTR1 silencing inhibits angiogenesis by limiting copper entry into endothelial cells
Gomathy Narayanan1, Bharathidevi S R, Harish Vuyyuru
1R. S. Mehta Jain Department of Biochemistry and Cell Biology, Vision Research Foundation, Chennai, India ; Birla Institute of Technology and Science, Pilani (Rajasthan), India.
Abstract:
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.
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