|Ephrin-A4 Is Involved in Retinal Neovascularization by Regulating the VEGF Signaling Pathway|
|Du, Wei; Yu, Wenzhen; Huang, Lvzhen; Zhao, Min; Li, Xiaoxin|
|刊名||INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE|
|WOS标题词||Science & Technology|
|关键词[WOS]||ENDOTHELIAL-GROWTH-FACTOR ; EPHA RECEPTOR ; OCULAR NEOVASCULARIZATION ; INDUCED ANGIOGENESIS ; A4 EXPRESSION ; ANIMAL-MODELS ; RETINOPATHY ; MICE ; OSTEOSARCOMA ; INTERFERENCE|
PURPOSE. Retinal neovascularization (NV) is a major cause of blindness. Recent research suggests that factors other than VEGF participate in this process. This study aimed to determine the role of ephrin-A4 in retinal NV.
METHODS. The expression and effect of ephrin-A4 was investigated in a mouse model of oxygen-induced retinopathy (OIR) and the RF/6A retina endothelial cell line. Ephrin-A4 expression and VEGF signaling pathway phosphorylation were determined by PCR, immunohistochemistry, and western blot analyses. ShRNA was used to silence ephrin-A4 in vitro and in vivo. Retinal flat mounts and tube formation assays were performed to evaluate ephrin-A4 function in the NV process in vivo and in vitro.
RESULTS. Ephrin-A4 was overexpressed in the retina of OIR mice and in RF/6A and RPE cells after CoCl2 stimulation. In vitro, Ephrin-A4/Fc treatment significantly increased the tube number of RF/6A cells on a membrane preparation and the phosphorylation levels of VEGR2, Akt1, and ERK1/2 in RF/6A cells. Moreover, ephrin-A4 knockout markedly suppressed pathologic neovascularization in vivo and inhibited the proliferation and tube formation capacity of RF/6A cells in vitro. Furthermore, in the absence of ephrin-A4, the phosphorylation of VEGFR2, Akt1, and ERK1/2 was defective under VEGF(165) stimulation, and the proangiogenic function of VEGF165 was also compromised.
CONCLUSIONS. This study suggests that ephrin-A4 plays an important role in retinal NV and is a potential target against retinal NV. The proangiogenic function of ephrin-A4 may be linked to its crucial role in the VEGF signaling pathway. (Invest Ophthalmol Vis Sci. 2012;53:1990-1998) DOI:10.1167/iovs.11-8788
|作者单位||Peking Univ, Peoples Hosp, Dept Ophthalmol, Key Lab Vis Loss & Restorat,Minist Educ, Beijing 100044, Peoples R China|
|Du, Wei,Yu, Wenzhen,Huang, Lvzhen,et al. Ephrin-A4 Is Involved in Retinal Neovascularization by Regulating the VEGF Signaling Pathway[J]. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE,2012,53(4):1990-1998.|
|APA||Du, Wei,Yu, Wenzhen,Huang, Lvzhen,Zhao, Min,&Li, Xiaoxin.(2012).Ephrin-A4 Is Involved in Retinal Neovascularization by Regulating the VEGF Signaling Pathway.INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE,53(4),1990-1998.|
|MLA||Du, Wei,et al."Ephrin-A4 Is Involved in Retinal Neovascularization by Regulating the VEGF Signaling Pathway".INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 53.4(2012):1990-1998.|