Extracellular Uridine Triphosphate and Adenosine Triphosphate Attenuate Endothelial Inflammation through miR-22-Mediated ICAM-1 Inhibition

Olof Gidlöf, Ramasri Sathanoori, Marco Magistri, Mohammad Ali Faghihi, Claes Wahlestedt, Björn Olde, David Erlinge

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Adenosine and uridine triphosphate (ATP and UTP) can act as extracellular signalling molecules, playing important roles in vascular biology and disease. ATP and UTP acting via the P2Y<inf>2</inf>-receptor have, for example, been shown to regulate endothelial dilatation, inflammation and angiogenesis. MicroRNAs (miRNAs), a class of regulatory, short, non-coding RNAs, have been shown to be important regulators of these biological processes. In this study, we used RNA deep-sequencing to explore changes in miRNA expression in the human microvascular endothelial cell line HMEC-1 upon UTP treatment. The expression of miR-22, which we have previously shown to target ICAM-1 mRNA in HMEC-1, increased significantly after stimulation. Up-regulation of miR-22 and down-regulation of cell surface ICAM-1 were confirmed with qRT-PCR and flow cytometry, respectively. siRNA-mediated knockdown of the P2Y<inf>2</inf>-receptor abolished the effect of UTP on miR-22 transcription. Leukocyte adhesion was significantly inhibited in HMEC-1 following miR-22 overexpression and treatment with UTP/ATP. In conclusion, extracellular UTP and ATP can attenuate ICAM-1 expression and leukocyte adhesion in endothelial cells through miR-22.

Original languageEnglish (US)
Pages (from-to)71-80
Number of pages10
JournalJournal of Vascular Research
DOIs
StateAccepted/In press - Jun 13 2015

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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