Yamagishi Sho-ichi, Matsui Takanori, Nakamura Kazuo, Yoshida Takafumi, Shimizu Kyoko, Takegami Yoshiaki, Shimizu Tadamichi, Inoue Hiroyoshi, Imaizumi Tsutomu
Department of Internal Medicine, Kurume University School of Medicine, Japan.
Microvasc Res. 2006 May;71(3):222-6. doi: 10.1016/j.mvr.2006.03.001. Epub 2006 Apr 19.
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.
血管紧张素II（Ang II）是肾素-血管紧张素系统的主要效应因子，可引发多种炎症增殖反应，从而参与血管生成。T细胞通过向炎症部位传递血管内皮生长因子（VEGF），在血管生成中也发挥着重要作用。由于我们之前已表明色素上皮衍生因子（PEDF）可阻断内皮细胞中的Ang II信号传导，因此我们在此研究了PEDF是否能抑制MOLT-3 T细胞中Ang-II诱导的VEGF表达，并探讨了PEDF抑制作用的潜在机制。Ang II显著上调了MOLT-3 T细胞中VEGF mRNA水平，而PEDF或奥美沙坦（一种Ang II 1型受体阻滞剂）可抑制这种上调。PEDF可阻断MOLT-3 T细胞中Ang-II诱导的活性氧（ROS）生成。此外，发现H(2)O(2)以剂量依赖方式上调MOLT-3 T细胞中VEGF mRNA水平。这些结果表明，PEDF可通过抑制ROS生成来抑制MOLT-3 T细胞中Ang-II诱导的VEGF表达。PEDF对T细胞中VEGF表达的阻断作用可能成为病理性血管生成的新治疗靶点。
