Dada Shirine, Demartines Nicolas, Dormond Olivier
Transplantation Biology Center, Children's Hospital Boston, Harvard Medical School, USA.
Biochem Biophys Res Commun. 2008 Aug 8;372(4):875-9. doi: 10.1016/j.bbrc.2008.05.154. Epub 2008 Jun 6.
Prostaglandin E(2) (PGE(2)) promotes angiogenesis by in part inducing endothelial cell survival and migration. The present study examined the role of mTOR and its two complexes, mTORC1 and mTORC2, in PGE(2)-mediated endothelial cell responses. We used small interfering RNA (siRNA) to raptor or rictor to block mTORC1 or mTORC2, respectively. We observed that down-regulation of mTORC2 but not mTORC1 reduced baseline and PGE(2)-induced endothelial cell survival and migration. At the molecular level, we found that knockdown of mTORC2 inhibited PGE(2)-mediated Rac and Akt activation two important signaling intermediaries in endothelial cell migration and survival, respectively. In addition, inhibition of mTORC2 by prolonged exposure of endothelial cells to rapamycin also prevented PGE(2)-mediated endothelial cell survival and migration confirming the results obtained with the siRNA approach. Taken together these results show that mTORC2 but not mTORC1 is an important signaling intermediary in PGE(2)-mediated endothelial cell responses.
前列腺素E(2)（PGE(2)）部分通过诱导内皮细胞存活和迁移来促进血管生成。本研究检测了mTOR及其两个复合物mTORC1和mTORC2在PGE(2)介导的内皮细胞反应中的作用。我们分别使用针对raptor或rictor的小干扰RNA（siRNA）来阻断mTORC1或mTORC2。我们观察到，下调mTORC2而非mTORC1会降低基线水平以及PGE(2)诱导的内皮细胞存活和迁移。在分子水平上，我们发现敲低mTORC2会抑制PGE(2)介导的Rac和Akt激活，这两者分别是内皮细胞迁移和存活中的两个重要信号传导中间体。此外，通过使内皮细胞长期暴露于雷帕霉素来抑制mTORC2，也会阻止PGE(2)介导的内皮细胞存活和迁移，这证实了通过siRNA方法获得的结果。综上所述，这些结果表明，mTORC2而非mTORC1是PGE(2)介导的内皮细胞反应中的重要信号传导中间体。
