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

Lena Pitzler, Markus Auler, Kristina Probst, Christian Frie, Vera Bergmeier, Tatjana Holzer, Daniele Belluoccio, Jocelyn Van der Bergen, Julia Etich, Harald Ehlen, Zhigang Zhou, Wolfgang Bielke, Ernst Poschl, Mats Paulsson, Bent Brachvogel

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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.
Original languageEnglish
Pages (from-to)1297-1309
Number of pages13
JournalStem Cells
Volume34
Issue number5
Early online date9 Mar 2016
DOIs
Publication statusPublished - May 2016

Keywords

  • Perivascular cells
  • miRNA
  • miR-126-3p
  • angiogenesis
  • Spred1
  • Plk2
  • Tlr3

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