miR‐126‐3p Promotes Matrix‐Dependent Perivascular Cell Attachment, Migration and Intercellular Interaction

• Published in: Stem cells (Dayton, Ohio) Vol. 34; no. 5; pp. 1297 - 1309
• Main Authors: Pitzler, Lena, Auler, Markus, Probst, Kristina, Frie, Christian, Bergmeier, Vera, Holzer, Tatjana, Belluoccio, Daniele, van den Bergen, Jocelyn, Etich, Julia, Ehlen, Harald, Zhou, Zhigang, Bielke, Wolfgang, Pöschl, Ernst, Paulsson, Mats, Brachvogel, Bent
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.05.2016
• Subjects: Angiogenesis; Animals; Blood Vessels - cytology; Cell Adhesion - drug effects; Cell Adhesion - genetics; Cell Communication - drug effects; Cell Communication - genetics; Cell Movement - drug effects; Cell Movement - genetics; Cell Shape - drug effects; Chemokines - metabolism; Coculture Techniques; Collagen - pharmacology; Drug Combinations; Extracellular Matrix - drug effects; Extracellular Matrix - metabolism; Extracellular Signal-Regulated MAP Kinases - metabolism; Gene Silencing - drug effects; Human Umbilical Vein Endothelial Cells - cytology; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Laminin - pharmacology; MAP Kinase Signaling System - drug effects; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; miR‐126‐3p; Neovascularization, Physiologic - genetics; Perivascular cells; Plk2; Proteoglycans - pharmacology; Spred1; Tlr3; Transcriptome - genetics; Up-Regulation - drug effects; Up-Regulation - genetics; Angiogenesis; Perivascular cells; Plk2; miRNA; miR-126-3p; Spred1; Tlr3
• ISSN: 1066-5099; 1549-4918
• DOI: 10.1002/stem.2308

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 EC. 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. Stem Cells 2016;34:1297–1309