The RNA-binding protein quaking maintains endothelial barrier function and affects VE-cadherin and β-catenin protein expression.
The RNA-binding protein quaking maintains endothelial barrier function and affects VE-cadherin and β-catenin protein expression.
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DOI：
10.1038/srep21643
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发表时间：
2016-02-24
影响因子：
4.6
通讯作者：
van Gils JM
中科院分区：
文献类型：
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作者：
de Bruin RG;van der Veer EP;Prins J;Lee DH;Dane MJ;Zhang H;Roeten MK;Bijkerk R;de Boer HC;Rabelink TJ;van Zonneveld AJ;van Gils JM
适当调节内皮细胞-细胞接触对内皮细胞的生理功能至关重要。内皮间连接积极参与控制血管渗漏、白细胞渗出和血管生成的开始和进展。我们发现rna结合蛋白quaking在内皮细胞中高度表达，并且在层流下长时间培养和转录因子KLF2结合启动子使其表达增强。此外，我们还证明了震动直接结合VE-cadherin和β-catenin的mRNA，并可以诱导这些基因的3'UTR介导的mRNA翻译。在体外，降低震动水平可减弱VE-cadherin和β-catenin的表达和内皮屏障功能，并导致体内缓激肽诱导的血管渗漏增加。综上所述，我们报道震动在维持内皮屏障功能中是必不可少的。我们的研究结果对转录后调控在控制血管完整性中的重要性提供了新的见解。
Proper regulation of endothelial cell-cell contacts is essential for physiological functioning of the endothelium. Interendothelial junctions are actively involved in the control of vascular leakage, leukocyte diapedesis, and the initiation and progression of angiogenesis. We found that the RNA-binding protein quaking is highly expressed by endothelial cells, and that its expression was augmented by prolonged culture under laminar flow and the transcription factor KLF2 binding to the promoter. Moreover, we demonstrated that quaking directly binds to the mRNA of VE-cadherin and β-catenin and can induce mRNA translation mediated by the 3′UTR of these genes. Reduced quaking levels attenuated VE-cadherin and β-catenin expression and endothelial barrier function in vitro and resulted in increased bradykinin-induced vascular leakage in vivo. Taken together, we report that quaking is essential in maintaining endothelial barrier function. Our results provide novel insight into the importance of post-transcriptional regulation in controlling vascular integrity.