CXCR1 and CXCR2 silencing modulates CXCL8-dependent endothelial cell proliferation, migration and capillary-like structure formation.
CXCR1 and CXCR2 silencing modulates CXCL8-dependent endothelial cell proliferation, migration and capillary-like structure formation.
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DOI：
10.1016/j.mvr.2011.06.011
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发表时间：
2011-11
影响因子：
3.1
通讯作者：
Singh RK
中科院分区：
文献类型：
--
作者：
Singh S;Wu S;Varney M;Singh AP;Singh RK
CXCR1和CXCR2是血管生成ELR+ CXC趋化因子的受体，在内皮细胞上有差异表达；然而，它们在血管生成中的功能意义尚不清楚。在本研究中，我们通过短发夹RNA （shRNA）敲低人微血管内皮细胞（HMEC-1）中CXCR1和/或CXCR2的表达，确定了这些受体在调节内皮细胞表型中的功能意义。观察细胞增殖、迁移、侵袭及毛细血管样结构（CLS）的形成。我们的数据表明，敲低CXCR1和/或CXCR2的表达可抑制内皮细胞的增殖、存活、迁移、侵袭和CLS形成。此外，我们通过评估ERK磷酸化和细胞骨架重排来检测cxcl -8依赖性CXCR1和/或CXCR2介导的表型改变的机制，并观察到ERK磷酸化和细胞骨架重排在HMEC-1-shCXCR1、HMEC-1-shCXCR2和HMEC-1-shCXCR1/2细胞中的抑制作用。综上所述，这些数据表明，CXCR1和CXCR2的表达在调节人微血管内皮细胞的多种生物活性中起着关键作用。
CXCR1 and CXCR2 are receptors for angiogenic ELR+ CXC chemokines and are differentially expressed on endothelial cells; however, their functional significance in angiogenesis remains unclear. In this study, we determined the functional significance of these receptors in modulating endothelial cell phenotype by knocking-down the expression of CXCR1 and/or CXCR2 in human microvascular endothelial cells (HMEC-1) using short-hairpin RNA (shRNA). Cell proliferation, migration, invasion and capillary-like structure (CLS) formation were analyzed. Our data demonstrate that knock-down of CXCR1 and/or CXCR2 expression inhibited endothelial cell proliferation, survival, migration, invasion and CLS formation. Additionally, we examined the mechanism of CXCL-8-dependent CXCR1 and/or CXCR2 mediated phenotypic changes by evaluating ERK phosphorlyation and cytoskeletal rearrangement and observed inhibition of ERK phosphorylation and cytoskeletal rearrangement in HMEC-1-shCXCR1, HMEC-1-shCXCR2 and HMEC-1-shCXCR1/2 cells. Together, these data demonstrate that CXCR1 and CXCR2 expression plays a critical role in regulating multiple biological activities in human microvascular endothelial cells.
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影响因子：
6.4
作者：
Matsuo, Yoichi;Ochi, Nobuo;Sawai, Hirozumi;Yasuda, Akira;Takahashi, Hiroki;Fumahashi, Hitoshi;Takeyama, Hiromitsu;Tong, Zhimin;Guha, Sushovan
通讯作者：
Guha, Sushovan
影响因子：
4.4
作者：
Keane, MP;Belperio, JA;Strieter, RM
通讯作者：
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影响因子：
6.4
作者：
Matsuo, Yoichi;Raimondo, Massimo;Guha, Sushovan
通讯作者：
Guha, Sushovan
影响因子：
3.1
作者：
Li, AH;Dubey, S;Singh, RK
通讯作者：
Singh, RK
影响因子：
3.8
作者：
Murdoch, C;Monk, PN;Finn, A
通讯作者：
Finn, A