miR126-5p repression of ALCAM and SetD5 in endothelial cells regulates leucocyte adhesion and transmigration

miR126-5p is processed from the miR126-3p/-5p duplex, which is expressed in endothelial cells and gives rise to the guide strand miR126-3p and the passenger strand miR126-5p. miR126-3p has prominent roles in vascular development and diseases, whereas the expression and physiological functions of miR...

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Bibliographic Details
Published in:Cardiovascular research 2014-06, Vol.102 (3), p.436-447
Main Authors: Poissonnier, Loïc, Villain, Gaëlle, Soncin, Fabrice, Mattot, Virginie
Format: Article
Language:English
Subjects:
Animals
Antigens, CD - genetics
Cardiology and cardiovascular system
Cell Adhesion
Cell Adhesion Molecules, Neuronal - genetics
Cell Movement
Cells, Cultured
Endothelial Cells - physiology
Fetal Proteins - genetics
Gene Expression Regulation
Human health and pathology
Humans
Leukocytes - physiology
Life Sciences
Methyltransferases - genetics
Mice
MicroRNAs - physiology
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Summary:miR126-5p is processed from the miR126-3p/-5p duplex, which is expressed in endothelial cells and gives rise to the guide strand miR126-3p and the passenger strand miR126-5p. miR126-3p has prominent roles in vascular development and diseases, whereas the expression and physiological functions of miR126-5p are unknown. The purpose of this study was to evaluate the expression and role of miR126-5p in blood vessel endothelial cells. miR126-5p is mostly expressed in blood vessel endothelial cells in vivo and in vitro. Gain- and loss-of-function approaches revealed that miR126-5p promotes leucocyte adhesion and represses leucocyte transendothelial migration. Two distinct target genes of miR126-5p in endothelial cells were identified: the activated leucocyte cell adhesion molecule (ALCAM) gene which codes for an adhesion molecule involved in leucocyte transendothelial migration and SetD5, a gene with previously unknown functions. Using either a blocking antibody or target protectors which specifically disrupt the miRNA/mRNA target pairing, we showed that miR126-5p promotes leucocyte adhesion by controlling the expression of SetD5 and represses transendothelial migration via the regulation of ALCAM. miR126-5p controls ALCAM and SetD5 expression in vivo in separate tissues and regulates leucocyte infiltration into inflamed lungs by repressing ALCAM expression. miR126-5p is a functional, endothelial-enriched microRNA that participates in the control of leucocyte trafficking by regulating the expression of ALCAM and SetD5.
ISSN:0008-6363
1755-3245
DOI:10.1093/cvr/cvu040