title: 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.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Experimental Neonatology, Medical Faculty, University of Cologne, Cologne, Germany.|Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Pitzler
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Experimental Neonatology, Medical Faculty, University of Cologne, Cologne, Germany.|Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Auler
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Experimental Neonatology, Medical Faculty, University of Cologne, Cologne, Germany.|Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Probst
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Experimental Neonatology, Medical Faculty, University of Cologne, Cologne, Germany.|Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Frie
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Experimental Neonatology, Medical Faculty, University of Cologne, Cologne, Germany.|Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Bergmeier
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Experimental Neonatology, Medical Faculty, University of Cologne, Cologne, Germany.|Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Holzer
authors.affiliation: Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging - Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
authors.forename: Daniele
authors.initials: D
authors.lastname: Belluoccio
authors.affiliation: Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.|Murdoch Children's Research Institute, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: van den Bergen
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Experimental Neonatology, Medical Faculty, University of Cologne, Cologne, Germany.|Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Etich
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Experimental Neonatology, Medical Faculty, University of Cologne, Cologne, Germany.|Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Ehlen
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Mechernich, NRW, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bielke
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Ernst
authors.initials: E
authors.lastname: Pöschl
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany.|Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia.|Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, United Kingdom.
authors.forename: Mats
authors.initials: M
authors.lastname: Paulsson
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Experimental Neonatology, Medical Faculty, University of Cologne, Cologne, Germany.|Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany.
authors.forename: Bent
authors.initials: B
authors.lastname: Brachvogel
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000166:cytology*; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D002450:Cell Communication / Q000187:drug effects / Q000235:genetics*; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D048430:Cell Shape / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D018920:Coculture Techniques; D003094:Collagen / Q000494:pharmacology; D004338:Drug Combinations; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020868:Gene Silencing / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000235:genetics; D011509:Proteoglycans / Q000494:pharmacology; D059467:Transcriptome / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D018925:Chemokines; D004338:Drug Combinations; D007797:Laminin; D035683:MicroRNAs; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Angiogenesis; Perivascular cells; Plk2; Spred1; Tlr3; miR-126-3p; miRNA