Gene regulation of a novel angiogenesis inhibitor, vasohibin, in endothelial cells.
We recently reported that vasohibin is a negative feedback regulator of angiogenesis, and it is specifically expressed in endothelial cells. Here, we characterize the regulation of vasohibin expression. Two possible splicing variants were found, and the longer isoform was preferentially expressed. VEGF induced the expression of vasohibin, and this induction was abrogated by anti-VEGFR2 mAb but not by anti-VEGFR1 mAb. Pharmacological analysis revealed that the downstream targets of VEGFR2 were PKCs, especially PKCdelta. Actinomycin D did not alter the kinetics of vasohibin mRNA induction upon VEGF treatment, whereas cycloheximide completely abolished its induction. We tested the effect of various inflammatory cytokines on vasohibin expression. TNFalpha, IL1 and IFNgamma decreased VEGF-stimulated vasohibin expression. Actinomycin D did not alter the kinetics of vasohibin mRNA induction upon TNFalpha treatment. These results indicate that the expression of vasohibin in endothelial cells is regulated either positively or negatively by certain factors at the transcriptional level.
Shimizu
Kazue
K
Department of Vascular Biology, Institute of Development, Aging, and Cancer, Tohoku University, Sendai 980-575, Japan.
Watanabe
Kazuhide
K
Yamashita
Hiroshi
H
Abe
Mayumi
M
Yoshimatsu
Hironobu
H
Ohta
Hideki
H
Sonoda
Hikaru
H
Sato
Yasufumi
Y
D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D042783:Endothelial Cells / Q000378:metabolism*; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007700:Kinetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D020533:Angiogenesis Inhibitors; D018797:Cell Cycle Proteins; D016207:Cytokines; D016228:Endothelial Growth Factors; D011506:Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C493181:VASH1 protein, human; D003609:Dactinomycin; D003513:Cycloheximide; D040262:Receptors, Vascular Endothelial Growth Factor