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

Sci Rep. 2016 Feb 24;6:21643. doi: 10.1038/srep21643.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics*
  • Antigens, CD / metabolism
  • Cadherins / genetics*
  • Cadherins / metabolism
  • Capillary Permeability
  • Female
  • Gene Expression
  • HEK293 Cells
  • Human Umbilical Vein Endothelial Cells / physiology*
  • Humans
  • Kruppel-Like Transcription Factors / physiology
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Protein Binding
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / physiology*
  • Transcriptional Activation
  • beta Catenin / genetics*
  • beta Catenin / metabolism

Substances

  • Antigens, CD
  • CTNNB1 protein, human
  • Cadherins
  • KLF2 protein, human
  • Kruppel-Like Transcription Factors
  • QKI protein, human
  • RNA, Messenger
  • RNA-Binding Proteins
  • beta Catenin
  • cadherin 5