CXCR4 down-regulation by small interfering RNA inhibits invasion and tubule formation of human retinal microvascular endothelial cells

Keming Yu, Jing Zhuang, Joseph M. Kaminski, Bala Ambati, Qianying Gao, Ping Ma, Dongjiang Liao, Fan Li, Xuan Liu, Jian Ge

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The progressive alterations to the retinal microvasculature in diabetic retinopathy are known to cause vision loss. Chemokines are characterized by their ability to induce cell invasion, adhesion and migration. In this study, we used double siRNA transfection to transiently and selectively decrease the level of the endogenous CXCR4 in human retinal microvascular endothelial cells (HRMECs). The functional consequences of silencing CXCR4 expression in HRMECs were investigated using an endothelial cell migration assay and tubule formation in Matrigel. When CXCR4 expression was decreased with siRNA, HRMECs were less invasive and also resulted in markedly diminished vascular networks on Matrigel as compared to the controls. Additionally, hypoxia and VEGF, the factors affecting microvascular, regulate the expression level of CXCR4 in HRMECs, respectively, which have synergistic, additive effect in the HRMECs. As such, CXCR4 antagonists may become a therapeutic target for the treatment of retinal angiopathies.

Original languageEnglish (US)
Pages (from-to)990-996
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume358
Issue number4
DOIs
StatePublished - Jul 13 2007

Keywords

  • CXCR4
  • Human retinal microvascular endothelial cells
  • Hypoxia
  • VEGF
  • siRNA

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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