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MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts

Author

Listed:
  • Thomas Thum

    (Department of Medicine I,
    Junior Research Group, Interdisziplinäres Zentrum für Klinische Forschung (IZKF))

  • Carina Gross

    (Rudolf Virchow Center, Deutsche Forschungsgemeinschaft (DFG) Research Center for Experimental Biomedicine,)

  • Jan Fiedler

    (Department of Medicine I,
    Junior Research Group, Interdisziplinäres Zentrum für Klinische Forschung (IZKF))

  • Thomas Fischer

    (Rudolf Virchow Center, Deutsche Forschungsgemeinschaft (DFG) Research Center for Experimental Biomedicine,)

  • Stephan Kissler

    (Rudolf Virchow Center, Deutsche Forschungsgemeinschaft (DFG) Research Center for Experimental Biomedicine,)

  • Markus Bussen

    (University of California, San Francisco, California 94158, USA)

  • Paolo Galuppo

    (Department of Medicine I,)

  • Steffen Just

    (Department of Internal Medicine III,)

  • Wolfgang Rottbauer

    (Department of Internal Medicine III,)

  • Stefan Frantz

    (Department of Medicine I,)

  • Mirco Castoldi

    (Oncology and Immunology
    Molecular Medicine Partnership Unit, University of Heidelberg)

  • Jürgen Soutschek

    (Regulus Therapeutics, Carlsbad, California 92008, USA)

  • Victor Koteliansky

    (Alnylam Pharmaceuticals, Cambridge, Massachusetts 02142, USA)

  • Andreas Rosenwald

    (Institute of Pathology, University of Wuerzburg, 97080 Wuerzburg, Germany)

  • M. Albert Basson

    (King’s College)

  • Jonathan D. Licht

    (Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA)

  • John T. R. Pena

    (Laboratory of RNA Molecular Biology, Rockefeller University, New York, New York 10065, USA)

  • Sara H. Rouhanifard

    (Laboratory of RNA Molecular Biology, Rockefeller University, New York, New York 10065, USA)

  • Martina U. Muckenthaler

    (Oncology and Immunology
    Molecular Medicine Partnership Unit, University of Heidelberg)

  • Thomas Tuschl

    (Laboratory of RNA Molecular Biology, Rockefeller University, New York, New York 10065, USA)

  • Gail R. Martin

    (University of California, San Francisco, California 94158, USA)

  • Johann Bauersachs

    (Department of Medicine I,)

  • Stefan Engelhardt

    (Rudolf Virchow Center, Deutsche Forschungsgemeinschaft (DFG) Research Center for Experimental Biomedicine,
    Institute of Pharmacology and Toxicology, Technische Universitaet Muenchen (TUM))

Abstract

RNAi: targeting heart disease MicroRNAs, the small noncoding RNAs that regulate gene expression, have been shown to be expressed in cardiac muscle cells and their aberrant regulation was correlated with heart disease. Thum et al. have looked at how microRNAs in other heart cells may contribute to disease. They find that microRNA-21 (miR-21) is upregulated in cardiac fibroblasts in mouse models of heart disease. This activates a signalling pathway that exacerbates the extent of damage to the heart tissues. When miR-21 is silenced in vivo using a specific antisense oligonucleotide (an anti-miR-21 antagomir), heart failure can be prevented. In addition, giving mice anti-miR-21 after established heart failure appeared to reverse some of the tissue damage. This work validates miR-21 as a disease target in heart failure and illustrates the broad therapeutic potential of microRNA modulation.

Suggested Citation

  • Thomas Thum & Carina Gross & Jan Fiedler & Thomas Fischer & Stephan Kissler & Markus Bussen & Paolo Galuppo & Steffen Just & Wolfgang Rottbauer & Stefan Frantz & Mirco Castoldi & Jürgen Soutschek & Vi, 2008. "MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts," Nature, Nature, vol. 456(7224), pages 980-984, December.
    • Handle: RePEc:nat:nature:v:456:y:2008:i:7224:d:10.1038_nature07511
    DOI: 10.1038/nature07511
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    Cited by:

    1. Charlotte Glinge & Sebastian Clauss & Kim Boddum & Reza Jabbari & Javad Jabbari & Bjarke Risgaard & Philipp Tomsits & Bianca Hildebrand & Stefan Kääb & Reza Wakili & Thomas Jespersen & Jacob Tfelt-Han, 2017. "Stability of Circulating Blood-Based MicroRNAs – Pre-Analytic Methodological Considerations," PLOS ONE, Public Library of Science, vol. 12(2), pages 1-16, February.
    2. Li Li & Chang Liu & Fang Wang & Wei Miao & Jie Zhang & Zhiqian Kang & Yihan Chen & Luying Peng, 2014. "Unraveling the Hidden Heterogeneities of Breast Cancer Based on Functional miRNA Cluster," PLOS ONE, Public Library of Science, vol. 9(1), pages 1-6, January.

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