Molecular Immunology Unit, Hospital Universitario Puerta de Hierro, 28222 Majadahonda, Madrid, Spain.
Exp Cell Res. 2012 Feb 15;318(4):371-8. doi: 10.1016/j.yexcr.2011.12.005. Epub 2011 Dec 14.
The Slit family of secreted proteins acts through the Roundabout (Robo) receptors to repel axonal migration during central nervous system development. Emerging evidence shows that Slit/Robo interactions also play a role in angiogenesis. The effect of Robo signaling on endothelial cells has been shown to be context-dependent. However, the role of Slit/Robo in pericytes has been largely unexplored. The aim of this study was to determine the effect of Slit2 on primary human pericytes and to address the underlying mechanisms, including the receptors potentially implicated. We demonstrate that both Robo1 and Robo4 are expressed by human pericytes. In the presence of their ligand Slit2, spontaneous and PDGF-induced migration of pericytes was impaired. This antimigratory activity of Slit-2 correlated with the inhibition of actin-based protrusive structures. Interestingly, human pericyte interaction with immobilized Slit2 was inhibited in the presence of anti-Robo1 and anti-Robo4 blocking antibodies, suggesting the implication of both receptors. These results add new insights into the role of Slit proteins during the angiogenic process that relies on the directional migration not only of endothelial cells but also of pericytes.
Slit 家族分泌蛋白通过 Roundabout（Robo）受体发挥作用，在中枢神经系统发育过程中排斥轴突迁移。新出现的证据表明，Slit/Robo 相互作用在血管生成中也起着作用。Robo 信号对内皮细胞的影响被证明是依赖于上下文的。然而，Slit/Robo 在周细胞中的作用在很大程度上尚未被探索。本研究旨在确定 Slit2 对原代人周细胞的影响，并探讨潜在涉及的受体的潜在机制。我们证明 Robo1 和 Robo4 均由人周细胞表达。在配体 Slit2 的存在下，周细胞的自发和 PDGF 诱导迁移受到损害。Slit-2 的这种抗迁移活性与肌动蛋白基突起结构的抑制相关。有趣的是，在存在抗 Robo1 和抗 Robo4 阻断抗体的情况下，与人周细胞与固定化 Slit2 的相互作用被抑制，表明这两种受体都有涉及。这些结果为 Slit 蛋白在血管生成过程中的作用提供了新的见解，该过程不仅依赖于内皮细胞的定向迁移，还依赖于周细胞的定向迁移。
