CXCR4 down-regulation by small interfering RNA inhibits invasion and tubule formation of human retinal microvascular endothelial cells.
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.
Yu
Keming
K
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, PR China.
Zhuang
Jing
J
Kaminski
Joseph M
JM
Ambati
Bala
B
Gao
Qianying
Q
Ma
Ping
P
Liao
Dongjiang
D
Li
Fan
F
Liu
Xuan
X
Ge
Jian
J
D001808:Blood Vessels / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D020868:Gene Silencing / Q000502:physiology; D006801:Humans; D018919:Neovascularization, Physiologic / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D012171:Retinal Vessels / Q000166:cytology* / Q000378:metabolism*
D034741:RNA, Small Interfering; D019718:Receptors, CXCR4