MiR-134-mediated β1 integrin expression and function in mesenchymal stem cells

David M. Poitz, Friedrich Stölzel, Laleh Arabanian, Jens Friedrichs, Denitsa Docheva, Matthias Schieker, Fernando A Fierro, Uwe Platzbecker, Rainer Ordemann, Carsten Werner, Martin Bornhäuser, Ruth H. Strasser, Gerhard Ehninger, Thomas Illmer

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3396-3404
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1833
Issue number12
DOIs
StatePublished - Dec 2013

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Keywords

  • β1 integrin
  • CD29
  • MDS
  • Mesenchymal stem cells
  • MicroRNA
  • MiR-134
  • Myelodysplastic Syndrome
  • SCP-1

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Poitz, D. M., Stölzel, F., Arabanian, L., Friedrichs, J., Docheva, D., Schieker, M., Fierro, F. A., Platzbecker, U., Ordemann, R., Werner, C., Bornhäuser, M., Strasser, R. H., Ehninger, G., & Illmer, T. (2013). MiR-134-mediated β1 integrin expression and function in mesenchymal stem cells. Biochimica et Biophysica Acta - Molecular Cell Research, 1833(12), 3396-3404. https://doi.org/10.1016/j.bbamcr.2013.10.003