Inhibition of vascular permeability factor/vascular endothelial growth factor-mediated angiogenesis by the Kruppel-like factor KLF2.
The Kruppel-like factor KLF2 was recently identified as a novel regulator of endothelial pro-inflammatory and pro-thrombotic function. Here it is shown that overexpression of KLF2 potently inhibits vascular permeability factor/vascular endothelial growth factor (VEGF-A)-mediated angiogenesis and tissue edema in the nude ear mouse model of angiogenesis. In vitro, KLF2 expression retards VEGF-mediated calcium flux, proliferation and induction of pro-inflammatory factors in endothelial cells. This effect is due to a potent inhibition of VEGFR2/KDR expression and promoter activity. These observations identify KLF2 as a regulator of VEGFR2/KDR and provide a foundation for novel approaches to regulate angiogenesis.
Program in Cardiovascular Transcriptional Biology, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Resham
R
Bhattacharya
Sucharita
S
Senbanerjee
Zhiyong
Z
Lin
Samy
S
Mir
Anne
A
Hamik
Ping
P
Wang
Priyabrata
P
Mukherjee
Debabrata
D
Mukhopadhyay
Mukesh K
MK
Jain
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D051741:Kruppel-Like Transcription Factors; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic; D013927:Thrombosis; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D016335:Zinc Fingers
C096161:KLF2 protein, human; C498314:Klf2 protein, mouse; D051741:Kruppel-Like Transcription Factors; D015534:Trans-Activators; D042461:Vascular Endothelial Growth Factor A; D049452:Green Fluorescent Proteins; D002118:Calcium