VEGF differentially activates STAT3 in microvascular endothelial cells
VEGF differentially activates STAT3 in microvascular endothelial cells
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DOI：
10.1096/fj.02-1084fje
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发表时间：
2003-06-01
期刊：
影响因子：
4.8
通讯作者：
Caldwell, RB
中科院分区：
文献类型：
--
作者：
Bartoli, M;Platt, DH;Caldwell, RB
在以异常血管生成为特征的几种病理中发现VEGF表达增加。已有研究表明转录因子STAT 3介导VEGF基因的转录和激活。在这项研究中，Western分析和共聚焦免疫细胞化学被用来检查STAT 3在视网膜微血管内皮细胞（BREC）的激活。我们发现VEGF快速诱导STAT 3酪氨酸磷酸化和核转位。免疫沉淀研究还表明，VEGF与VEGFR 2仅在BREC中形成复合物，而不在主动脉大血管内皮细胞（BAEC）中形成复合物。此外，VEGF诱导的VEGF表达的定量实时RT-PCR分析显示，仅在BREC中特异性mRNA形成显著增加，而在BAEC中不增加，并且这种作用通过反义介导的STAT 3表达减少而显著降低。此外，在人真皮微血管内皮细胞（HDMEC）中进行的研究表明，在这种内皮细胞类型中，VEGF自分泌表达也伴随着STAT 3激活，如在BREC中一样。在这项研究中，我们发现VEGF可以在微血管内皮细胞与大血管内皮细胞中差异诱导STAT 3活化，并且这种作用与VEGFR 2/STAT 3复合物的形成有关，这与VEGF自分泌刺激其自身基因表达的能力相关。
Increased VEGF expression is found in several pathologies characterized by abnormal angiogenesis. Previous studies have shown that the transcription factor STAT3 mediates VEGF gene transcription and its activation. In this study, Western analysis and confocal immunocytochemistry were used to examine STAT3 activation in retinal microvascular endothelial cells (BREC). We found that VEGF rapidly induces STAT3 tyrosine phosphorylation and nuclear translocation. Immunoprecipitation studies also showed that VEGF forms a complex with VEGFR2 only in BREC and not in aortic macrovascular endothelial cells (BAEC). In addition, quantitative real-time RT-PCR analysis of VEGF-induced VEGF expression showed a significant increase in specific mRNA formation only in BREC and not in BAEC, and this effect was significantly reduced by antisense-mediated reduction of STAT3 expression. Furthermore, studies conducted in human dermal microvascular endothelial cells (HDMEC) showed that, in this endothelial cell type, VEGF autocrine expression is also accompanied by STAT3 activation as in BREC. In this study we showed that VEGF can differentially induce STAT3 activation in micro-versus macro-vascular endothelial cells and that this effect is linked to VEGFR2/STAT3 complex formation, which correlates with VEGF autocrine ability to stimulate its own gene expression.