CXCL12 enhances angiogenesis through CXCR7 activation in human umbilical vein endothelial cells.
CXCL12 enhances angiogenesis through CXCR7 activation in human umbilical vein endothelial cells.
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CXCL12 通过激活人脐静脉内皮细胞中的 CXCR7 增强血管生成
DOI：
10.1038/s41598-017-08840-y
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发表时间：
2017-08-15
影响因子：
4.6
通讯作者：
Jiang L
中科院分区：
文献类型：
--
作者：
Zhang M;Qiu L;Zhang Y;Xu D;Zheng JC;Jiang L
血管生成是从现有血管网络形成新血管的过程。人脐静脉内皮细胞（HUVECs）可能有助于血管修复和血管生成的研究。趋化因子CXCL 12主要通过其受体CXCR 4调节多种细胞功能，包括血管生成。与CXCL 12/CXCR 4相反，很少有研究描述CXCR 7在血管生物学中的作用，CXCR 7在血管生成中的下游机制仍不清楚。本研究的结果表明，CXCL 12剂量依赖性地增强绒毛尿囊膜（CAM）和HUVEC中的血管生成。TC 14012（一种CXCR 7激动剂）特异性激活CXCR 7导致显著诱导HUVECs和体内的管形成。进一步的证据表明，CXCL 12诱导了HUVECs的定向极化和迁移，这是管形成所必需的。此外，CXCR 7易位过程中观察到的极化的HUVECs在条纹测定。最后，用TC 14012处理也显著增加PI 3 K/Akt磷酸化，并且通过用Akt抑制剂处理HUVEC来阻断管形成。总之，这项研究表明，CXCL 12刺激的CXCR 7作为一种功能性受体，激活Akt，促进HUVEC中的血管生成，CXCR 7可能是血管损伤后内皮再生和修复的潜在靶分子。
Angiogenesis is the process by which new vessels form from existing vascular networks. Human umbilical vein endothelial cells (HUVECs) may contribute to the study of vascular repair and angiogenesis. The chemokine CXCL12 regulates multiple cell functions, including angiogenesis, mainly through its receptor CXCR4. In contrast to CXCL12/CXCR4, few studies have described roles for CXCR7 in vascular biology, and the downstream mechanism of CXCR7 in angiogenesis remains unclear. The results of the present study showed that CXCL12 dose-dependently enhanced angiogenesis in chorioallantoic membranes (CAMs) and HUVECs. The specific activation of CXCR7 with TC14012 (a CXCR7 agonist) resulted in the significant induction of tube formation in HUVECs andin vivo. Further evidence suggested that CXCL12 induced directional polarization and migration in the HUVECs, which is necessary for tube formation. Moreover, CXCR7 translocalization was observed during the polarization of HUVECs in stripe assays. Finally, treatment with TC14012 also significantly increased PI3K/Akt phosphorylation, and tube formation was blocked by treating HUVECs with an Akt inhibitor. Overall, this study indicated that CXCL12-stimulated CXCR7 acts as a functional receptor to activate Akt for angiogenesis in HUVECs and that CXCR7 may be a potential target molecule for endothelial regeneration and repair after vascular injury.
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DOI：
10.1084/jem.20102010
发表时间：
2011-02-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cruz-Orengo L;Holman DW;Dorsey D;Zhou L;Zhang P;Wright M;McCandless EE;Patel JR;Luker GD;Littman DR;Russell JH;Klein RS
通讯作者：
Klein RS
影响因子：
9.7
作者：
Rahimi, Massod;Toth, Theodore A.;Tang, Careen K.
通讯作者：
Tang, Careen K.
DOI：
10.1038/nrm3176
发表时间：
2011-08-23
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
--
作者：
Liu, An-Heng;Cao, Ya-Nan;Wang, Xiao-Ming
通讯作者：
Wang, Xiao-Ming
血管生成素通过 PI-3K/Akt 通路促进内皮细胞增殖
影响因子：
--
作者：
Chen, Zhong;Liu, Fang;Han, Zhongchao
通讯作者：
Han, Zhongchao