首页> 外文期刊>Journal of Neurochemistry: Offical Journal of the International Society for Neurochemistry >Endothelin-1 increases the expression of VEGF-R1/Flt-1 receptors in rat cultured astrocytes through ETB receptors
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Endothelin-1 increases the expression of VEGF-R1/Flt-1 receptors in rat cultured astrocytes through ETB receptors

机译:内皮素-1通过ETB受体增加大鼠培养的星形胶质细胞中VEGF-R1 / Flt-1受体的表达

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Expressions of vascular endothelial growth factor (VEGF) receptors in astrocytes are increased in damaged brains. To clarify the regulatory mechanisms of VEGF receptors, the effects of endothelin-1 (ET-1) were examined in rat cultured astrocytes. Expressions of VEGF-R1 and -R2 receptor mRNA were at similar levels, whereas the mRNA expressions of VEGF-R3 and Tie-2, a receptor for angiopoietins, were lower. Placenta growth factor, a selective agonist of the VEGF-R1 receptor, induced phosphorylation of focal adhesion kinase (FAK) and extracellular signal regulated kinase 1/2 (ERK1/2). Phosphorylations of FAK and ERK 1/2 were also stimulated by VEGF-E, a selective VEGF-R2 agonist. Increased phosphorylations of FAK and ERK1/2 by VEGF(165) were reduced by selective antagonists for VEGF-R1 and -R2. Treatment with ET-1 increased VEGF-R1 mRNA and protein levels. The effects of ET-1 on VEGF-R1 mRNA were mimicked by Ala(1,3,11,15)-ET-1, a selective agonist for ETB receptors, and inhibited by BQ788, an ETB antagonist. ET-1 did not affect the mRNA levels of VEGF-R2, -R3, and Tie-2. Pre-treatment with ET-1 potentiated the effects of placenta growth factor on phosphorylations of FAK and ERK1/2. These findings suggest that ET-1 induces up-regulation of VEGF-R1 receptors in astrocytes, and potentiates VEGF signals in damaged nerve tissues.
机译:在受损的大脑中星形胶质细胞中血管内皮生长因子(VEGF)受体的表达增加。为了阐明VEGF受体的调控机制,在大鼠培养的星形胶质细胞中检查了内皮素-1(ET-1)的作用。 VEGF-R1和-R2受体mRNA的表达水平相似,而血管生成素受体VEGF-R3和Tie-2的mRNA表达则较低。胎盘生长因子是VEGF-R1受体的选择性激动剂,可诱导粘着斑激酶(FAK)和细胞外信号调节激酶1/2(ERK1 / 2)磷酸化。 FAK和ERK 1/2的磷酸化也受到选择性VEGF-R2激动剂VEGF-E的刺激。 VEGF-R1和-R2的选择性拮抗剂可减少VEGF(165)增强的FAK和ERK1 / 2磷酸化。 ET-1处理可增加VEGF-R1 mRNA和蛋白水平。 ET-1对VEGF-R1 mRNA的作用被Ela受体选择性激动剂Ala(1,3,11,15)-ET-1模仿,并被ETB拮抗剂BQ788抑制。 ET-1不会影响VEGF-R2,-R3和Tie-2的mRNA水平。 ET-1预处理可增强胎盘生长因子对FAK和ERK1 / 2磷酸化的影响。这些发现表明,ET-1诱导星形胶质细胞中VEGF-R1受体的上调,并增强受损神经组织中的VEGF信号。

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