Endothelial connexin32 enhances angiogenesis by positively regulating tube formation and cell migration.
Endothelial connexin32 enhances angiogenesis by positively regulating tube formation and cell migration.
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DOI：
10.1016/j.yexcr.2013.12.002
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发表时间：
2014-02
影响因子：
3.7
通讯作者：
Takayuki Okamoto;N. Akita;E. Kawamoto;Tatsuya Hayashi;Koji Suzuki;M. Shimaoka
中科院分区：
文献类型：
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作者：
Takayuki Okamoto;N. Akita;E. Kawamoto;Tatsuya Hayashi;Koji Suzuki;M. Shimaoka
间隙连接蛋白 connexin32 (Cx32)、Cx37、Cx40 和 Cx43 在内皮细胞中表达，调节涉及炎症、血管发生和血管重塑的血管功能。异常的 Cxs 表达促进动脉粥样硬化的发展，而动脉粥样硬化是由血管生成调节的；然而，内皮细胞 Cxs 在血管生成中所起的作用仍不清楚。在这项研究中，我们确定了内皮 Cxs（尤其是 Cx32）对血管生成的影响。与过度表达 Cx37、Cx40 和 Cx43 的 Cx 转染细胞或模拟处理的细胞相比，转染过度表达 Cx32 的 EA.hy926 细胞显着增加毛细血管长度和分支数量。与对照相比，通过细胞内转移抗 Cx32 抗体的治疗抑制了人脐静脉内皮细胞 (HUVEC) 的管形成。体外伤口愈合测定表明，Cx32 转染细胞显着增加了修复面积，而抗 Cx32 抗体处理的 HUVEC 则减少了修复面积。离体主动脉环测定和体内基质胶斑块测定表明，Cx32 缺陷小鼠损害了血管萌发。主动脉和细胞迁移到植入的基质胶中。因此，内皮 Cx32 促进管形成、伤口愈合、血管萌芽和细胞迁移。我们的结果表明，内皮细胞 Cx32 通过增强内皮细胞管形成和细胞迁移来正向调节血管生成。
The gap junction proteins connexin32 (Cx32), Cx37, Cx40, and Cx43 are expressed in endothelial cells, and regulate vascular functions involving inflammation, vasculogenesis and vascular remodeling. Aberrant Cxs expression promotes the development of atherosclerosis which is modulated by angiogenesis; however the role played by endothelial Cxs in angiogenesis remains unclear. In this study, we determined the effects of endothelial Cxs, particularly Cx32, on angiogenesis. EA.hy926 cells that had been transfected to overexpress Cx32 significantly increased capillary length and the number on branches compared to Cx-transfectant cells over-expressing Cx37, Cx40, and Cx43 or mock-treated cells. Treatmentviaintracellular transfer of anti-Cx32 antibody suppressed tube formation of human umbilical vein endothelial cells (HUVECs) compared to controls.In vitrowound healing assays revealed that Cx32-transfectant cells significantly increased the repaired area while anti-Cx32 antibody-treated HUVECs reduced it.Ex vivoaorta ring assays andin vivomatrigel plaque assays showed that Cx32-deficient mice impaired both vascular sprouting from the aorta and cell migration into the implanted matrigel. Therefore endothelial Cx32 facilitates tube formation, wound healing, vascular sprouting, and cell migration. Our results suggest that endothelial Cx32 positively regulates angiogenesis by enhancing endothelial cell tube formation and cell migration.