Pigment-epithelium-derived factor (PEDF) inhibits angiotensin-II-induced vascular endothelial growth factor (VEGF) expression in MOLT-3 T cells through anti-oxidative properties.
Angiotensin II (Ang II), the dominant effector of the renin-angiotensin system, elicits numerous inflammatory-proliferative responses, thereby being involved in angiogenesis. T cells play an important role in angiogenesis as well by delivering vascular endothelial growth factor (VEGF) to inflammatory sites. Since we have previously shown that pigment-epithelium-derived factor (PEDF) blocks the Ang II signaling in endothelial cells, we studied here whether PEDF could inhibit the Ang-II-induced VEGF expression in MOLT-3 T and examined the potential mechanism of PEDF inhibitory effects. Ang II significantly up-regulated VEGF mRNA levels in MOLT-3 T cells, which was inhibited by PEDF or olmesartan, an Ang II type 1 receptor blocker. PEDF blocked the Ang-II-induced reactive oxygen species (ROS) generation in MOLT-3 T cells. Furthermore, H(2)O(2) was found to up-regulate VEGF mRNA levels in MOLT-3 T cells in a dose-dependent manner. These results demonstrate that PEDF could inhibit the Ang-II-induced VEGF expression in MOLT-3 T cells via suppression of ROS generation. Blockade by PEDF of VEGF expression in T cells may become a novel therapeutic target for pathological angiogenesis.
Yamagishi
Sho-ichi
S
Department of Internal Medicine, Kurume University School of Medicine, Japan. shoichi@med.kurume-u.ac.jp
Matsui
Takanori
T
Nakamura
Kazuo
K
Yoshida
Takafumi
T
Shimizu
Kyoko
K
Takegami
Yoshiaki
Y
Shimizu
Tadamichi
T
Inoue
Hiroyoshi
H
Imaizumi
Tsutomu
T
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D001483:Base Sequence; D002460:Cell Line; D005136:Eye Proteins / Q000494:pharmacology*; D006801:Humans; D009154:Mutation; D009414:Nerve Growth Factors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015843:Serpins / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D020830:rac1 GTP-Binding Protein / Q000235:genetics; D000099174:Pigment Epithelium-Derived Factor
D000804:Angiotensin II; D005136:Eye Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D020830:rac1 GTP-Binding Protein; D000099174:Pigment Epithelium-Derived Factor; C107953:RAC1 protein, human