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

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 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 SIGNIFICANCE STATEMENTIncreased miR-126-3p levels stimulate matrix-dependent intercellular interaction of perivascular cells to promote PVC coverage of newly formed endothelial vessel and transform immature vessels into mature, less permeable vessels. In contrast, decreased miR-126-3p levels may loosen BM-dependent intercellular connections and support detachment of PVC and EC from preexisting vessels to allow new blood vessel formation. We therefore propose that miR-126-3p is a novel regulator of PVC-mediated vessel stability during neoangiogenesis and in pathological scenarios like tumor angiogenesis.

The differences in brain stem transcriptional profiling in hypertensive ISIAH and normotensive WAG rats

“…The current study demonstrated that Tlr3 is upregulated in brain stem of ISIAH rats. Earlier it was shown that TLR3 expression may be stimulated to modulate cell-cell and cell-matrix contacts of perivascular cells playing a role in angiogenesis and blood vessels permeability [53].…”

Calmodulin Regulated Spectrin Associated Protein 1 mRNA is Directly Regulated by miR‐126 in Primary Human Osteoblasts

“…Furthermore, a number of miRNAs, such as miR-223, miR-155, and miR-21, were found to be upregulated in mature osteoblasts, influencing osteoclastogenesis, and regulating the production of extracellular matrix and, thus, bone mass (see [Lian et al, 2012] and [Taipaleenmaki et al, 2012] for review). miR-126 is a well-studied molecule which has been chiefly associated with regulation of angiogenesis and vascular integrity [Fish et al, 2008;Wang et al, 2008;Zhang et al, 2013;Chen et al, 2016;Pitzler et al, 2016]. Interestingly, the data from our laboratory show that miR-126 has anti-angiogenic properties in peripheral blood endothelial progenitor cells [Goerke et al, 2015].…”

“…miR‐126 is a well‐studied molecule which has been chiefly associated with regulation of angiogenesis and vascular integrity [Fish et al, ; Wang et al, ; Zhang et al, ; Chen et al, ; Pitzler et al, ]. Interestingly, the data from our laboratory show that miR‐126 has anti‐angiogenic properties in peripheral blood endothelial progenitor cells [Goerke et al, ].…”

The key miRNAs for metastasis and survival of colon adenocarcinoma

“…Overexpression of hsa-mir-126-3p can promote cell proliferation and migration by activating PI3K/AKT signaling pathway (29). Hsa-mir-126-3p is reported as a novel regulator of PVC-mediated vessel stability during tumor angiogenesis (30). The expression of hsa-mir-126-3p is increased in patients with lung adenocarcinoma.…”