title: Extracellular Uridine Triphosphate and Adenosine Triphosphate Attenuate Endothelial Inflammation through miR-22-Mediated ICAM-1 Inhibition.
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 P2Y2-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 P2Y2-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.
authors.affiliation: Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Olof
authors.initials: O
authors.lastname: Gidlöf
authors.forename: Ramasri
authors.initials: R
authors.lastname: Sathanoori
authors.forename: Marco
authors.initials: M
authors.lastname: Magistri
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Faghihi
authors.forename: Claes
authors.initials: C
authors.lastname: Wahlestedt
authors.forename: Björn
authors.initials: B
authors.lastname: Olde
authors.forename: David
authors.initials: D
authors.lastname: Erlinge
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism*; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D058912:Purinergic P2Y Receptor Agonists / Q000494:pharmacology*; D034622:RNA Interference; D058473:Receptors, Purinergic P2Y2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D014544:Uridine Triphosphate / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; C573420:ICAM1 protein, human; C548375:MIRN22 microRNA, human; D035683:MicroRNAs; D058912:Purinergic P2Y Receptor Agonists; D058473:Receptors, Purinergic P2Y2; D018799:Intercellular Adhesion Molecule-1; D000255:Adenosine Triphosphate; D014544:Uridine Triphosphate