Inhibition of VEGF expression by targeting HIF-1 alpha with small interference RNA in human RPE cells.
BACKGROUND
Vascular endothelial growth factor (VEGF) is upregulated by hypoxia and is a major stimulatory factor for choroidal neovascularization. The upregulation of VEGF expression in response to hypoxia occurs through hypoxia-inducible factor 1 (HIF-1), which is a transcription factor that regulates genes involved in the response to hypoxia. HIF-1 alpha is the inducible subunit of the HIF-1.


OBJECTIVE
To further define HIF-1 function in angiogenesis and to explore novel approaches to modulate choroidal neovascularization in age-related macular degeneration.


METHODS
In this study, we examined the response of human retinal pigment epithelium (RPE) cells to hypoxia and employed the small interference RNA technique to knock down gene expression of HIF-1 alpha in RPE cells.


RESULTS
We found that both the mRNA and protein levels of HIF-1 alpha in the RPE cells increased in response to hypoxia, followed by increasing expression of VEGF. Both the mRNA and protein levels of HIF-1 alpha and VEGF in the RPE cells were decreased dramatically after transfection with a HIF-1 alpha-specific small interference RNA vector.


CONCLUSIONS
Our results suggest that HIF-1 may be involved in angiogenesis by controlling the expression of VEGF in vivo and provide a possible strategy for the treatment of angiogenesis by targeting the HIF-1 alpha in ischemic retinopathies.
Zhang
Peng
P
Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, PR China.
Wang
Yusheng
Y
Hui
Yannian
Y
Hu
Dan
D
Wang
Haiyan
H
Zhou
Jian
J
Du
Hongjun
H
D015153:Blotting, Western; D002478:Cells, Cultured; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D051793:Hypoxia-Inducible Factor 1; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A