TY - JOUR
T1 - Gene regulation of a novel angiogenesis inhibitor, vasohibin, in endothelial cells
AU - Shimizu, Kazue
AU - Watanabe, Kazuhide
AU - Yamashita, Hiroshi
AU - Abe, Mayumi
AU - Yoshimatsu, Hironobu
AU - Ohta, Hideki
AU - Sonoda, Hikaru
AU - Sato, Yasufumi
N1 - Funding Information:
This work was supported by the Japan Society of the Promotion of Science Research for the Future (Grant No. 99L01304) and by a Grant-in-Aid for Scientific Research on Priority Areas of the Japanese Ministry of Education, Science, Sports and Culture (Grant No. 16022205).
PY - 2005/2/18
Y1 - 2005/2/18
N2 - 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 PKCδ. 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. TNFα, IL1 and IFNγ decreased VEGF-stimulated vasohibin expression. Actinomycin D did not alter the kinetics of vasohibin mRNA induction upon TNFα 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.
AB - 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 PKCδ. 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. TNFα, IL1 and IFNγ decreased VEGF-stimulated vasohibin expression. Actinomycin D did not alter the kinetics of vasohibin mRNA induction upon TNFα 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.
KW - Angiogenesis inhibitor
KW - Endothelial cell
KW - Induction
KW - PKC
KW - VEGF
KW - Vasohibin
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U2 - 10.1016/j.bbrc.2004.12.073
DO - 10.1016/j.bbrc.2004.12.073
M3 - Article
C2 - 15649403
AN - SCOPUS:11844283414
VL - 327
SP - 700
EP - 706
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -