title: The 106b∼25 microRNA cluster is essential for neovascularization after hindlimb ischaemia in mice.
abstract: OBJECTIVE
  MicroRNAs (miRNAs, miR) are endogenous short RNA sequences that regulate a wide range of physiological and pathophysiological processes. Several miRNAs control the formation of new blood vessels either by increasing or by inhibiting angiogenesis. Here, we investigated the possible role of the miR-106b∼25 cluster in postnatal neovascularization and in regulation of the angiogenic properties of adult bone marrow-derived stromal cells.
  
  
  RESULTS
  To study the effect of miR-106b∼25 deletion on neovascularization, we used a miR-106b∼25 knockout (KO) mouse model. After inducing hindlimb ischaemia, we showed that vascularization in ischaemic mice devoid of miR-106b∼25 is impaired, as evident from the reduced blood flow on laser Doppler perfusion imaging. The miR-106b∼25 cluster was also shown here to be an essential player in the proper functioning of bone marrow-derived stromal cells through its regulation of apoptosis, matrigel tube formation capacity, cytokine secretion, and expression of the stem-cell marker Sca-1. In addition, we showed that capillary sprouting from miR-106b∼25 KO aortic rings is diminished.
  
  
  CONCLUSIONS
  These results show that the miR-106b∼25 cluster regulates post-ischaemic neovascularization in mice, and that it does so in part by regulating the function of angiogenic bone marrow-derived stromal cells and of endothelial cells.
authors: Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Jonathan
authors: J
authors: Semo
authors: Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Rinat
authors: R
authors: Sharir
authors: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Arnon
authors: A
authors: Afek
authors: Department of Pathology, Chaim Sheba Medical Center, Ramat Gan, Israel.
authors: Camila
authors: C
authors: Avivi
authors: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Department of Pathology, Chaim Sheba Medical Center, Ramat Gan, Israel.
authors: Iris
authors: I
authors: Barshack
authors: Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors: Sofia
authors: S
authors: Maysel-Auslender
authors: The Laboratory for Applied Cancer Research, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors: Yakov
authors: Y
authors: Krelin
authors: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: David
authors: D
authors: Kain
authors: Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors: Michal
authors: M
authors: Entin-Meer
authors: Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors: Gad
authors: G
authors: Keren
authors: The Heart Institute, Kaplan Medical Center, PO Box 1, 76100 Rehovot, Israel affiliated to the Faculty of Medicine, Hebrew University, Jerusalem, Israel jgeorge@bezeqint.net.
authors: Jacob
authors: J
authors: George
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000950:Antigens, Ly / Q000378:metabolism; D001011:Aorta / Q000502:physiology; D017209:Apoptosis / Q000502:physiology; D001783:Blood Flow Velocity / Q000502:physiology; D001854:Bone Marrow Cells / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D042783:Endothelial Cells / Q000502:physiology; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia / Q000503:physiopathology; D008565:Membrane Proteins / Q000378:metabolism; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019899:Paracrine Communication / Q000502:physiology; D010455:Peptides / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D017154:Stromal Cells / Q000502:physiology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000950:Antigens, Ly; D006023:Glycoproteins; C074650:Ly6a protein, mouse; C558895:MIRN25 microRNA, mouse; D008565:Membrane Proteins; D035683:MicroRNAs; C543896:Mirn106 microRNA, mouse; D010455:Peptides; D019009:Proto-Oncogene Proteins c-kit; D040301:Vascular Endothelial Growth Factor Receptor-2; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Angiogenesis; MicroRNAs