Regulation of vascular endothelial growth factor gene under hypoxia by using artificial transcription factors.
The vascular endothelial growth factor A (VEGF-A) gene is an attractive therapeutic target because both activation and repression of the gene are useful for treatment or cure of many diseases related to abnormal angiogenesis. To up- or downregulate the endogenous gene expression at will, we previously designed a 6-finger AZP to recognize a 19-bp target DNA in the VEGF-A gene, and fused the AZP with a nuclear localization signal and a transcriptional regulatory domain to generate artificial transcription factors (ATFs) for VEGF-A. Using the ATFs, we previously demonstrated efficient modulation of the endogenous VEGF-A expression under normoxia. In the present study, we examined whether these ATFs modulate the endogenous VEGF-A gene expression under hypoxic conditions as well. Enzyme-linked immunosorbent assays revealed that the gene-delivered ATFs up- or downregulated the VEGF-A expression efficiently under hypoxia.
Mori
Tomoaki
T
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Kyoto 615-8510, Japan.
Sasaki
Jun
J
Aoyama
Yasuhiro
Y
Sera
Takashi
T
D015687:Cell Hypoxia; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics*
D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A