title: MiR-134-mediated β1 integrin expression and function in mesenchymal stem cells.
abstract: The composition of the hematopoietic stem cell (HSC) niche within the bone marrow is highly dynamic, tightly regulated, and of importance for various HSC properties. Integrins are important molecules within this niche that influence those properties through the interactions of HSCs and mesenchymal stem cells (MSCs). Here we investigated the function of miR-134 in integrin regulation in MSCs. In MSCs, miR-134 post-transcriptionally regulated β1 integrin expression. This negative regulation of β1 integrin was mediated by the binding of miR-134 to its 3' untranslated region, which contains two conserved binding sites for miR-134. The miR-134-mediated silencing of β1 integrin in MSCs was shown by atomic force microscopy to decrease the adhesion of 32D cells to MSCs transfected with miR-134. Furthermore, the adhesion of MSCs to fibronectin was reduced after transfection with miR-134. MSCs from patients with myelodysplastic syndrome (MDS) revealed highly significant miR-134 overexpression compared with MSCs from healthy bone marrow donors. MSCs from MDS patients showed lower β1 integrin protein, but not lower mRNA, expression, suggesting post-transcriptional regulation. The present study demonstrates miR-134-mediated negative regulation of β1 integrin that influences cell adhesion to and of MSCs. These results further contribute to our understanding of the complexity of MDS.
authors.affiliation: Department of Internal Medicine and Cardiology, University of Technologies Dresden, Germany. Electronic address: david.poitz@tu-dresden.de.
authors.forename: David M
authors.initials: DM
authors.lastname: Poitz
authors.affiliation: Internal Medicine Department I, University Hospital Carl Gustav Carus Dresden, University of Technologies Dresden, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Stölzel
authors.affiliation: Internal Medicine Department I, University Hospital Carl Gustav Carus Dresden, University of Technologies Dresden, Germany.
authors.forename: Laleh
authors.initials: L
authors.lastname: Arabanian
authors.affiliation: Institute for Biofunctional Polymer Materials Dresden, Leibniz Institute of Polymer Research, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Friedrichs
authors.affiliation: Experimental Surgery and Regenerative Medicine, Department of Surgery, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Denitsa
authors.initials: D
authors.lastname: Docheva
authors.affiliation: Experimental Surgery and Regenerative Medicine, Department of Surgery, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schieker
authors.affiliation: Institute for Regenerative Cures, University of California, Davis, California, USA.
authors.forename: Fernando A
authors.initials: FA
authors.lastname: Fierro
authors.affiliation: Internal Medicine Department I, University Hospital Carl Gustav Carus Dresden, University of Technologies Dresden, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Platzbecker
authors.affiliation: Internal Medicine Department I, University Hospital Carl Gustav Carus Dresden, University of Technologies Dresden, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Ordemann
authors.affiliation: DFG Research Center and Cluster of Excellence for Regenerative Therapies Dresden (CRTD), Germany; Institute for Biofunctional Polymer Materials Dresden, Leibniz Institute of Polymer Research, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Werner
authors.affiliation: Internal Medicine Department I, University Hospital Carl Gustav Carus Dresden, University of Technologies Dresden, Germany; DFG Research Center and Cluster of Excellence for Regenerative Therapies Dresden (CRTD), Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
authors.affiliation: Department of Internal Medicine and Cardiology, University of Technologies Dresden, Germany.
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Strasser
authors.affiliation: Internal Medicine Department I, University Hospital Carl Gustav Carus Dresden, University of Technologies Dresden, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.affiliation: Internal Medicine Department I, University Hospital Carl Gustav Carus Dresden, University of Technologies Dresden, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Illmer
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001665:Binding Sites; D002448:Cell Adhesion / Q000235:genetics; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000473:pathology; D011485:Protein Binding / Q000235:genetics; D014162:Transfection; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D019012:Integrin beta1; C569273:MIRN134 microRNA, human; D035683:MicroRNAs
keywords: CD29; MDS; Mesenchymal stem cells; Myelodysplastic Syndrome; SCP-1; miR-134; microRNA; β1 integrin