Department of Cardiology, Cardiovascular Research Institute, Shenyang Northern Hospital, Shenyang, China.
Exp Cell Res. 2011 Dec 10;317(20):2904-13. doi: 10.1016/j.yexcr.2011.08.012. Epub 2011 Sep 9.
The migration of vascular endothelial cells plays a critical role in a variety of vascular physiological and pathological processes, such as embryonic development, angiogenesis, wound healing, re-endothelialization, and vascular remodeling. This study clarified the role and mechanism of a new vascular homeostasis regulator, Cellular repressor of E1A-stimulated genes (CREG), in the migration of primary human umbilical vein endothelial cells (HUVECs). A wound healing assay and transwell migration model showed that upregulation of CREG expression induced HUVEC migration and it was positively correlated with the expression of vascular endothelial growth factor. Furthermore, wild type integrin-linked kinase reversed the poor mobility of CREG knock-down HUVECs; in contrast, kinase-dead integrin-linked kinase weakened the migration of HUVECs. We also studied the effect of CREG on HUVEC migration by the addition of an mTOR inhibitor, recombinant vascular endothelial growth factor(165), neutralizing antibody of vascular endothelial growth factor(165) and AKT siRNA, and we concluded that CREG induces endothelial cell migration by activating the integrin-linked kinase/AKT/mTOR/VEGF(165) signaling pathway.
血管内皮细胞的迁移在多种血管生理和病理过程中起着关键作用，如胚胎发育、血管生成、伤口愈合、再内皮化和血管重塑。本研究阐明了新的血管稳态调节剂细胞 E1A 刺激基因抑制因子（CREG）在原代人脐静脉内皮细胞（HUVEC）迁移中的作用和机制。划痕愈合实验和 Transwell 迁移模型表明，CREG 表达上调诱导 HUVEC 迁移，且与血管内皮生长因子表达呈正相关。此外，野生型整合素连接激酶逆转了 CREG 敲低 HUVEC 较差的迁移能力；相反，激酶失活的整合素连接激酶削弱了 HUVEC 的迁移能力。我们还通过添加 mTOR 抑制剂、重组血管内皮生长因子（165）、血管内皮生长因子（165）中和抗体和 AKT siRNA 研究了 CREG 对 HUVEC 迁移的影响，结论是 CREG 通过激活整合素连接激酶/AKT/mTOR/VEGF（165）信号通路诱导内皮细胞迁移。
