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

Thomas Thum, Carina Gross, Jan Fiedler, Thomas Fischer, Stephan Kissler, Markus Bussen, Paolo Galuppo, Steffen Just, Wolfgang Rottbauer, Stefan Frantz, Mirco Castoldi, Jürgen Soutschek, Victor Koteliansky, Andreas Rosenwald, M. Albert Basson, Jonathan D. Licht, John T. R. Pena, Sara H. Rouhanifard, Martina U. Muckenthaler, Thomas Tuschl, Gail R. Martin, Johann Bauersachs () and Stefan Engelhardt ()
Additional contact information
Thomas Thum: Department of Medicine I,
Carina Gross: Rudolf Virchow Center, Deutsche Forschungsgemeinschaft (DFG) Research Center for Experimental Biomedicine,
Jan Fiedler: Department of Medicine I,
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
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
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,

Nature, 2008, vol. 456, issue 7224, 980-984

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.

Date: 2008
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DOI: 10.1038/nature07511

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