Translational regulation of vascular endothelial growth factor expression in renal epithelial cells by angiotensin II
Translational regulation of vascular endothelial growth factor expression in renal epithelial cells by angiotensin II
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DOI：
10.1152/ajprenal.00271.2004
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发表时间：
2005-03-01
影响因子：
4.2
通讯作者：
Kasinath, BS
中科院分区：
文献类型：
--
作者：
Feliers, D;Duraisamy, S;Kasinath, BS
血管紧张素II对肾上皮细胞血管内皮生长因子表达的翻译调节。美国肾脏生理学杂志288：F521-F529，2005年。首次发表于2004年11月30日; doi：10.1152/ ajprenal.00271.2004。血管紧张素II调节肾脏中生长因子的表达。我们研究了血管紧张素II是否调节近端肾小管上皮细胞（MCT）中血管内皮生长因子（VEGF）的合成。ANG II（1 nM）在5分钟内增加VEGF蛋白表达，效果持续30分钟。VEGF mRNA水平或mRNA稳定性没有变化，转录抑制剂不影响ANG II诱导的VEGF表达。研究了VEGF翻译的调节。多聚核糖体分析显示，选择性富集的重核糖体（多聚核糖体）与VEGF mRNA转录本相比，在ANG II处理的细胞中的轻核糖体，虽然GAPDH的分布是不变的。在体外翻译的总RNA从多核糖体组分显示选择性增加血管紧张素II治疗的细胞中VEGF蛋白的合成。PI 3激酶抑制剂LY-294002预孵育或显性阴性Akt表达可阻止ANG II刺激的VEGF翻译增加。ANG 11增加真核起始因子4 E及其结合蛋白4 E-BP 1的磷酸化，这是调节蛋白质翻译起始阶段的关键事件。ANG 11不能增加稳定表达4 E-BP 1磷酸化突变体的细胞中VEGF mRNA的翻译。我们的数据表明，血管内皮生长因子蛋白表达的快速增加，由血管紧张素11调节在肾上皮细胞中的血管内皮生长因子mRNA的翻译的起始阶段。ANG 11对VEGF翻译的调节代表了肾脏对损伤反应的一种新途径。
Translational regulation of vascular endothelial growth factor expression in renal epithelial cells by angiotensin II. Am J Physiol Renal Physiol 288: F521-F529, 2005. First published November 30, 2004; doi:10.1152/ ajprenal.00271.2004.-ANG II regulates growth factor expression in the kidney. We investigated whether ANG II regulated vascular endothelial growth factor (VEGF) synthesis in proximal tubular epithelial (MCT) cells. ANG II (1 nM) increased VEGF protein expression within 5 min, the effect lasting for 30 min. There was no change in VEGF mRNA levels or mRNA stability, and transcription inhibitors did not affect ANG II-induced VEGF expression. Regulation of VEGF translation was investigated. Polyribosomal analysis revealed selective enrichment of heavy ribosomes (polysomes) with VEGF mRNA transcripts compared with light ribosomes in ANG II-treated cells, although distribution of GAPDH was unaltered. In vitro translation of total RNA from polysomal fractions showed selective increase in VEGF protein synthesis in ANG II-treated cells. Preincubation with LY-294002, a PI 3-kinase inhibitor, or expression of dominant-negative Akt prevented ANG II-stimulated increase in VEGF translation. ANG 11 increased phosphorylation of eukaryouic initiation factor 4E and its binding protein 4E-BP1, critical events that regulate the initiation phase of protein translation. ANG 11 failed to increase VEGF mRNA translation in cells stably expressing the phosphorylation mutant of 4E-BP1. Our data illustrate that a rapid increase in VEGF protein expression by ANG 11 is regulated at the initiation phase of translation of VEGF mRNA in renal epithelial cells. Regulation of VEGF translation by ANG 11 represents a novel pathway of renal response to injury.