β2-Glycoprotein I inhibits endothelial cell migration through the nuclear factor κB signalling pathway and endothelial nitric oxide synthase activation
β2-Glycoprotein I inhibits endothelial cell migration through the nuclear factor κB signalling pathway and endothelial nitric oxide synthase activation
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DOI：
10.1042/bj20111383
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发表时间：
2012-07-01
影响因子：
4.1
通讯作者：
Chiang, An-Na
中科院分区：
文献类型：
--
作者：
Chiu, Wen-Chin;Chiou, Tzeon-Jye;Chiang, An-Na
β（2）-GPI（β（2）-glycoprotein I）是一种血浆糖蛋白，具有抗血管生成的功能;然而，其在细胞迁移中的生物学作用和分子基础仍不清楚。本研究的目的是评估β（2）-GPI对HAEC（人主动脉内皮细胞）迁移的贡献及其潜在机制的细节。使用伤口愈合和Boyden室测定，我们发现β（2）-GPI抑制内皮细胞迁移，其中和抗体恢复。NF-κ B（核因子κ B）抑制剂和NF-κ B的慢病毒siRNA（小干扰RNA）沉默显著减弱了对细胞迁移的抑制作用。此外，发现β（2）-GPI诱导I κ B α（NF-κ B的抑制剂）磷酸化和p65和p50的易位。我们进一步证明，β 2-GPI可增加eNOS [内皮NO（一氧化氮）合酶]的mRNA和蛋白水平以及NO的产生，而NF-κ B抑制剂和p65和p50的siRNA可显著抑制这些作用。此外，β（2）-GPI介导的细胞迁移抑制被eNOS抑制剂和eNOS siRNA逆转。本研究的发现为β（2）-GPI主要通过NF-κ B/eNOS/NO信号通路抑制内皮细胞迁移的能力提供了新的见解，这为血管疾病的临床治疗指明了潜在的方向。
beta(2)-GPI (beta(2)-glycoprotein I) is a plasma glycoprotein ascribed with an anti-angiogenic function; however, the biological role and molecular basis of its action in cell migration remain unknown. The aim of the present study was to assess the contribution of beta(2)-GPI to HAEC (human aortic endothelial cell) migration and the details of its underlying mechanism. Using wound healing and Boyden chamber assays, we found that beta(2)-GPI inhibited endothelial cell migration, which was restored by its neutralizing antibody. NF-kappa B (nuclear factor kappa B) inhibitors and lentiviral siRNA (small interfering RNA) silencing of NF-kappa B significantly attenuated the inhibitory effect of on cell migration. Moreover, beta(2)-GPI was found to induce I kappa B alpha (inhibitor of NF-kappa B) phosphorylation and translocation of p65 and p50. We further demonstrated that mRNA and protein levels of eNOS [endothelial NO (nitric oxide) synthase] and NO production were all increased by beta(2)-GPI and these effects were remarkably inhibited by NF-kappa B inhibitors and siRNAs of p65 and p50. Furthermore, beta(2)-GPI-mediated inhibition of cell migration was reversed by eNOS inhibitors and eNOS siRNAs. The findings of the present study provide novel insight into the ability of beta(2)-GPI to inhibit endothelial cell migration predominantly through the NF-kappa B/eNOS/NO signalling pathway, which indicates a potential direction for clinical therapy in vascular diseases.