miR-126-3p promotes matrix-dependent perivascular cell attachment, migration and intercellular interaction

Pitzler, Lena, Auler, Markus, Probst, Kristina, Frie, Christian, Bergmeier, Vera, Holzer, Tatjana, Belluoccio, Daniele, Van der Bergen, Jocelyn, Etich, Julia, Ehlen, Harald, Zhou, Zhigang, Bielke, Wolfgang, Poschl, Ernst, Paulsson, Mats and Brachvogel, Bent (2016) miR-126-3p promotes matrix-dependent perivascular cell attachment, migration and intercellular interaction. Stem Cells, 34 (5). pp. 1297-1309. ISSN 1066-5099

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Abstract

microRNAs (miRNAs) can regulate the interplay between perivascular cells (PVC) and endothelial cells (EC) during angiogenesis, but the relevant PVC-specific miRNAs are not yet defined. Here, we identified miR-126-3p and miR-146a to be exclusively upregulated in PVC upon interaction with EC, determined their influence on the PVC phenotype and elucidate their molecular mechanisms of action. Specifically the increase of miR-126-3p strongly promoted the motility of PVC on the basement membrane-like composite and stabilized networks of endothelial cells. Subsequent miRNA target analysis showed that miR-126-3p inhibits SPRED1 and PLK2 expression, induces ERK1/2 phosphorylation and stimulates TLR3 expression to modulate cell-cell and cell-matrix contacts of PVC. Gain of expression experiments in vivo demonstrated that miR-126-3p stimulates PVC coverage of newly formed vessels and transform immature into mature, less permeable vessels. In conclusion we showed that miR-126-3p regulates matrix-dependent PVC migration and intercellular interaction to modulate vascular integrity.

Item Type: Article
Uncontrolled Keywords: perivascular cells,mirna,mir-126-3p,angiogenesis,spred1,plk2,tlr3
Faculty \ School: Faculty of Science > School of Biological Sciences
Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 26 Apr 2016 10:00
Last Modified: 17 Mar 2020 21:36
URI: https://ueaeprints.uea.ac.uk/id/eprint/58369
DOI: 10.1002/stem.2308

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