title: miR-92a regulates angiogenic activity of adipose-derived mesenchymal stromal cells.
abstract: Mesenchymal stromal cells including those from adipose tissue (MSCs) regulate angiogenesis in adult tissues. MicroRNAs (miRs), small noncoding RNAs that control gene expression by binding to target mRNAs, reducing their stability and/or inhibiting translation, appear to be important regulators of blood vessel growth. In this study, we examined the impact of angio-miRs on paracrine activities of MSCs. Using Illumina microarrays we found that miR-92a is one of the most abundant angio-miRs in human MSCs. We transfected MSC with pre-miR-92a or anti-miR-92a which led to the coordinated changes of known miR-92a target mRNA levels. Then we tested the ability of conditioned medium from transfected cells to stimulate tube formation by HUVECs. MSC overexpressing miR-92a completely lost the ability to stimulate tubes formation by endothelial cells. However, knocking-out miR-92a by transfection with anti-miR-92a did not increase the ability of MSC to stimulate tube formation. Secretion of hepatocyte growth factor (HGF) and angiopoetin-1 was significantly lower in the medium of miR-92a overexpressing MSC, whereas VEGF secretion did not change significantly. The replenishment of HGF but not angiopoietin-1 has restored the ability of conditioned medium from miR-92a overexpressing MSC to stimulate the tube formation. We conclude that overexpression of miR-92a in MSC suppresses angiogenic properties of these cells by down-regulation of HGF secretion.
authors.affiliation: Faculty of Medicine, Lomonosov Moscow State University, 31-5 Lomonosovsky av, Moscow 119191 Russia. Electronic address: n_i_kalinina@mail.ru.
authors.forename: Natalia
authors.initials: N
authors.lastname: Kalinina
authors.affiliation: Faculty of Medicine, Lomonosov Moscow State University, 31-5 Lomonosovsky av, Moscow 119191 Russia. Electronic address: galkaklink@gmail.com.
authors.forename: Galina
authors.initials: G
authors.lastname: Klink
authors.affiliation: Faculty of Medicine, Lomonosov Moscow State University, 31-5 Lomonosovsky av, Moscow 119191 Russia. Electronic address: evgenglu@rambler.ru.
authors.forename: Eugeniy
authors.initials: E
authors.lastname: Glukhanyuk
authors.affiliation: Faculty of Medicine, Lomonosov Moscow State University, 31-5 Lomonosovsky av, Moscow 119191 Russia. Electronic address: t.lopatina@gmail.com.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Lopatina
authors.affiliation: Faculty of Medicine, Lomonosov Moscow State University, 31-5 Lomonosovsky av, Moscow 119191 Russia. Electronic address: efimenkoan@gmail.com.
authors.forename: Anastassia
authors.initials: A
authors.lastname: Efimenko
authors.affiliation: Faculty of Medicine, Lomonosov Moscow State University, 31-5 Lomonosovsky av, Moscow 119191 Russia. Electronic address: hanna@fbm.msu.ru.
authors.forename: Zhanna
authors.initials: Z
authors.lastname: Akopyan
authors.affiliation: Faculty of Medicine, Lomonosov Moscow State University, 31-5 Lomonosovsky av, Moscow 119191 Russia. Electronic address: tkachuk@fbm.msu.ru.
authors.forename: Vsevolod
authors.initials: V
authors.lastname: Tkachuk
mesh_terms: D000273:Adipose Tissue / Q000098:blood supply / Q000166:cytology* / Q000378:metabolism; D000328:Adult; D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D018919:Neovascularization, Physiologic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D017077:Culture Media, Conditioned; C066855:HGF protein, human; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor
keywords: Adipose-derived mesenchymal stromal cells; Angiogenesis; Growth factors; MiR-92a