Zheng Zhen-Zhong, Liu Zheng-Xiang
1095# JieFang Avenue, Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Int J Biochem Cell Biol. 2007;39(2):340-8. doi: 10.1016/j.biocel.2006.09.001. Epub 2006 Sep 14.
We previously reported that CD151 promotes neovascularization and improves blood perfusion in rat hind-limb ischemia model, but the precise mechanism is still unclear. Endothelial cell proliferation and cell migration play critical roles in angiogenesis. Many growth factors and hormones have been shown to regulate cell proliferation, cell migration and angiogenesis, including the activation of eNOS activity, via the PI3K/Akt signaling pathway. Whether CD151 induces cell proliferation and cell migration via PI3K/Akt signaling pathway is not known. Here we showed that CD151 promotes human umbilical vein endothelial cell (HUVEC) proliferation, migration and tube formation in vitro, accompanied by increased phosphorylation of Akt and eNOS, leading to increased eNOS activity and nitric oxide (NO) levels after rAAV-CD151 infection, whereas infection with rAAV-anti-CD151 attenuated the effects of CD151, which suggested that CD151 can activate PI3K/Akt pathway. Moreover, inhibitors of PI3K (LY294002) and eNOS (l-NAME) can attenuate CD151-induced cell proliferation and cell migration. The results suggested that activation of PI3K/Akt signaling pathway mediates CD151-induced cell proliferation and migration.
我们之前报道过，在大鼠后肢缺血模型中，CD151可促进新血管形成并改善血液灌注，但确切机制仍不清楚。内皮细胞增殖和细胞迁移在血管生成中起关键作用。许多生长因子和激素已被证明可通过PI3K/Akt信号通路调节细胞增殖、细胞迁移和血管生成，包括激活eNOS活性。CD151是否通过PI3K/Akt信号通路诱导细胞增殖和细胞迁移尚不清楚。在此我们表明，rAAV-CD151感染后，CD151可促进人脐静脉内皮细胞（HUVEC）的体外增殖、迁移和管腔形成，同时伴有Akt和eNOS磷酸化增加，导致eNOS活性和一氧化氮（NO）水平升高，而rAAV-抗CD151感染则减弱了CD151的作用，这表明CD151可激活PI3K/Akt通路。此外，PI3K抑制剂（LY294002）和eNOS抑制剂（L-NAME）可减弱CD151诱导的细胞增殖和细胞迁移。结果表明，PI3K/Akt信号通路的激活介导了CD151诱导的细胞增殖和迁移。
