title: The RNA-binding protein quaking maintains endothelial barrier function and affects VE-cadherin and β-catenin protein expression.
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.
authors.affiliation: Einthoven Laboratory of Experimental Vascular Medicine, Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Ruben G
authors.initials: RG
authors.lastname: de Bruin
authors.affiliation: Einthoven Laboratory of Experimental Vascular Medicine, Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Eric P
authors.initials: EP
authors.lastname: van der Veer
authors.affiliation: Einthoven Laboratory of Experimental Vascular Medicine, Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Jurriën
authors.initials: J
authors.lastname: Prins
authors.affiliation: Einthoven Laboratory of Experimental Vascular Medicine, Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Einthoven Laboratory of Experimental Vascular Medicine, Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Martijn J C
authors.initials: MJ
authors.lastname: Dane
authors.affiliation: Einthoven Laboratory of Experimental Vascular Medicine, Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Huayu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Einthoven Laboratory of Experimental Vascular Medicine, Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Marko K
authors.initials: MK
authors.lastname: Roeten
authors.affiliation: Einthoven Laboratory of Experimental Vascular Medicine, Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Roel
authors.initials: R
authors.lastname: Bijkerk
authors.affiliation: Einthoven Laboratory of Experimental Vascular Medicine, Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Hetty C
authors.initials: HC
authors.lastname: de Boer
authors.affiliation: Einthoven Laboratory of Experimental Vascular Medicine, Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Ton J
authors.initials: TJ
authors.lastname: Rabelink
authors.affiliation: Einthoven Laboratory of Experimental Vascular Medicine, Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Anton Jan
authors.initials: AJ
authors.lastname: van Zonneveld
authors.affiliation: Einthoven Laboratory of Experimental Vascular Medicine, Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Janine M
authors.initials: JM
authors.lastname: van Gils
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002199:Capillary Permeability; D005260:Female; D015870:Gene Expression; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000502:physiology*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000502:physiology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000502:physiology*; D015533:Transcriptional Activation; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D051176:beta Catenin; D000099152:Cadherin 5; C495270:CTNNB1 protein, human; C096161:KLF2 protein, human; C490832:QKI protein, human