Open AccessmiR‐126‐3p Promotes Matrix‐Dependent Perivascular Cell Attachment, Migration and Intercellular Interaction
Author(s) -
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
Publication year - 2016
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2308
Subject(s) - microbiology and biotechnology , biology , microrna , intracellular , matrix (chemical analysis) , basement membrane , motility , downregulation and upregulation , angiogenesis , cell , phosphorylation , cell migration , cancer research , chemistry , gene , biochemistry , chromatography
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. S tem C ells 2016;34:1297–1309