Nuclear translocation of phosphorylated STAT3 regulates VEGF-A-induced lymphatic endothelial cell migration and tube formation
Nuclear translocation of phosphorylated STAT3 regulates VEGF-A-induced lymphatic endothelial cell migration and tube formation
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DOI：
10.1016/j.bbrc.2011.07.111
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发表时间：
2011-09-02
影响因子：
3.1
通讯作者：
Sayama, Koji
中科院分区：
文献类型：
--
作者：
Okazaki, Hideki;Tokumaru, Sho;Sayama, Koji
血管内皮生长因子（VEGF）是调节内皮功能的内皮细胞特异性生长因子，并且已知信号转导子和转录激活子（STAT）在VEGF受体信号传导过程中是重要的。本研究的目的是确定STAT 3是否调节VEGF诱导的淋巴管内皮细胞（LEC）迁移和管形成。与对照组相比，VEGF-A（33 ng/ml）增强LEC迁移2倍，增加管长度25%，分别使用Boyden室和Matrigel测定分析。Western blot分析和免疫组化染色显示，VEGF-A可诱导磷酸化STAT 3在LEC中发生核转位，而这种转位可被表达STAT 3显性失活突变体（Ax-STAT 3F）的腺病毒载体转染LEC所阻断。Ax-STAT 3F转染也几乎完全抑制VEGF-A诱导的LEC迁移和管形成。这些结果表明，STAT 3是VEGF-A诱导的LEC迁移和管形成所必需的，并且STAT 3调节LEC功能。(C)2011 Elsevier Inc. All rights reserved.
Vascular endothelial growth factor (VEGF) is an endothelial cell-specific growth factor that regulates endothelial functions, and signal transducers and activators of transcription (STATs) are known to be important during VEGF receptor signaling. The aim of this study was to determine whether STAT3 regulates VEGF-induced lymphatic endothelial cell (LEC) migration and tube formation. VEGF-A (33 ng/ml) enhanced LEC migration by 2-fold and increased tube length by 25% compared with the control, as analyzed using a Boyden chamber and Matrigel assay, respectively. Western blot analysis and immunostaining revealed that VEGF-A induced the nuclear translocation of phosphorylated STAT3 in LECs, and this translocation was blocked by the transfection of LECs with an adenovirus vector expressing a dominant-negative mutant of STAT3 (Ax-STAT3F). Transfection with Ax-STAT3F also almost completely inhibited VEGF-A-induced LEC migration and tube formation. These results indicate that STAT3 is essential for VEGF-A-induced LEC migration and tube formation and that STAT3 regulates LEC functions. (C) 2011 Elsevier Inc. All rights reserved.