The RNA-binding protein quaking maintains endothelial barrier function and affects VE-cadherin and β-catenin protein expression

Scientific Reports
Ruben G de BruinJanine M van Gils

Abstract

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.

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Citations

Aug 16, 2018·American Journal of Physiology. Renal Physiology·Nima AbbasianAlan Bevington
Feb 12, 2019·Annual Review of Physiology·Xuri LiPeter Carmeliet
Nov 24, 2017·Physiological Reviews·Guy EelenPeter Carmeliet
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Feb 11, 2021·American Journal of Physiology. Lung Cellular and Molecular Physiology·Chen-Shan Chen WoodcockStephen Y Chan
Feb 27, 2021·The International Journal of Biochemistry & Cell Biology·Huayu ZhangJanine M van Gils
Mar 27, 2021·Nature Reviews. Nephrology·Sébastien J DumasPeter Carmeliet
Mar 30, 2021·Frontiers in Cell and Developmental Biology·Zi-Yi ZhouGuo-Rui Dou

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Methods Mentioned

BETA
PAR-CLIP
Protein Assay
transfection

Software Mentioned

QKI
ECIS

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