CREG1 promotes angiogenesis and neovascularization
CREG1 promotes angiogenesis and neovascularization
复制标题
CREG1促进血管生成和新血管形成
DOI：
10.2741/4272
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发表时间：
2014-06-01
影响因子：
3.1
通讯作者：
Han, Yaling
中科院分区：
文献类型：
--
作者：
Yan, Chenghui;Pu, Fang;Han, Yaling
长期以来，血管生成一直被认为是治疗缺血性损伤的重要策略。已有研究表明，E1a刺激基因的细胞抑制因子(CREG1)可促进人脐静脉内皮细胞(HUVEC)的增殖、迁移，保护内皮细胞(EC)免于凋亡。然而，其对血管生成的潜在作用仍不明确。在本研究中，我们研究了CREG1在促进血管生成中的作用和机制。我们发现，腺病毒转导的CREG1在人脐静脉内皮细胞中的表达增加了基质细胞内EC管的形成，并促进了移植到野生型小鼠体内的基质细胞塞的新生血管形成。此外，腺病毒CREG1的表达促进了丝状足的形成，同时伴随着整合素连接激酶(ILK)表达的增加及其下游效应器CDC42的激活。在CREG1杂合基因敲除小鼠中，股动脉结扎后后肢血流灌注显著减少。最后，将腺病毒CREG1肌肉注射到胃壁，部分恢复缺血后肢的血流灌注。我们的结果表明，CREG1通过激活ILK-CDC42促进EC丝状足的形成和血管组装，并促进新生血管的形成，这可能是缺血性损伤的治疗靶点。
Angiogenesis has long been considered as an important strategy for ischemic injury. It has been reported that cellular repressor of E1A-stimulated genes (CREG1) promotes human umbilical vein endothelial cell (HUVEC) proliferation, migration, and protects endothelial cell (EC) from apoptosis. However, its potential effect on angiogenesis remains undefined. In the present study, we investigated the role and mechanisms of CREG1 in promoting angiogenesis. We found that adenovirus-transduced CREG1 expression in HUVECs increases EC tube formation in matrigel and promotes neovascularization in matrigel plugs grafted into wild type mice. In addition, adenoviral CREG1 expression enhances filopodia formation, which is accompanied by increased expression of integrin-linked kinase (ILK) and activation of its downstream effector Cdc42. Hindlimb perfusion was significantly reduced after femoral artery ligation in CREG1 heterozygous knockout mice. Finally, adenoviral CREG1 was injected intramuscularly in gastrochemius and partially restores ischemic hindlimb perfusion. Our results demonstrated that CREG1 increases EC filopodia formation and vascular assembly via ILK-Cdc42 activation and promotes neovascularization, which might be a therapeutic target for ischemic injury.