Journal
STEM CELLS
Volume 34, Issue 5, Pages 1297-1309Publisher
WILEY
DOI: 10.1002/stem.2308
Keywords
Perivascular cells; miRNA; miR-126-3p; Angiogenesis; Spred1; Plk2; Tlr3
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Funding
- Medical Research Council [G0802553] Funding Source: researchfish
- MRC [G0802553] Funding Source: UKRI
- Medical Research Council [G0802553] Funding Source: Medline
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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.
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