MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts (original) (raw)
References
- Ambros, V. The functions of animal microRNAs. Nature 431, 350–355 (2004)
Article ADS CAS Google Scholar - Bartel, D. P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281–297 (2004)
Article CAS Google Scholar - Mi, S. et al. MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia. Proc. Natl Acad. Sci. USA 104, 19971–19976 (2007)
Article ADS CAS Google Scholar - He, L. et al. A microRNA component of the p53 tumour suppressor network. Nature 447, 1130–1134 (2007)
Article ADS CAS Google Scholar - Huang, J. et al. Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes. Nature Med. 13, 1241–1247 (2007)
Article CAS Google Scholar - Care, A. et al. MicroRNA-133 controls cardiac hypertrophy. Nature Med. 13, 613–618 (2007)
Article CAS Google Scholar - van Rooij, E. et al. Control of stress-dependent cardiac growth and gene expression by a microRNA. Science 316, 575–579 (2007)
Article ADS CAS Google Scholar - Yang, B. et al. The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2. Nature Med. 13, 486–491 (2007)
Article CAS Google Scholar - Zhao, Y. et al. Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2. Cell 129, 303–317 (2007)
Article CAS Google Scholar - Sayed, D., Hong, C., Chen, I. Y., Lypowy, J. & Abdellatif, M. MicroRNAs play an essential role in the development of cardiac hypertrophy. Circ. Res. 100, 416–424 (2007)
Article CAS Google Scholar - Engelhardt, S., Hein, L., Wiesmann, F. & Lohse, M. J. Progressive hypertrophy and heart failure in β1-adrenergic receptor transgenic mice. Proc. Natl Acad. Sci. USA 96, 7059–7064 (1999)
Article ADS CAS Google Scholar - Cheng, Y. H. et al. MicroRNAs are aberrantly expressed in hypertrophic heart — do they play a role in cardiac hypertrophy? Am. J. Pathol. 170, 1831–1840 (2007)
Article CAS Google Scholar - Tatsuguchi, M. et al. Expression of microRNAs is dynamically regulated during cardiomyocyte hypertrophy. J. Mol. Cell. Cardiol. 42, 1137–1141 (2007)
Article CAS Google Scholar - Sayed, D. et al. MicroRNA-21 targets Sprouty2 and promotes cellular outgrowths. Mol. Biol. Cell 19, 3272–3282 (2008)
Article CAS Google Scholar - Rockman, H. A. et al. Segregation of atrial-specific and inducible expression of an atrial natriuretic factor transgene in an in vivo murine model of cardiac hypertrophy. Proc. Natl Acad. Sci. USA 88, 8277–8281 (1991)
Article ADS CAS Google Scholar - Kudej, R. K. et al. Effects of chronic β-adrenergic receptor stimulation in mice. J. Mol. Cell. Cardiol. 29, 2735–2746 (1997)
Article CAS Google Scholar - Dudley, D. T., Pang, L., Decker, S. J., Bridges, A. J. & Saltiel, A. R. A synthetic inhibitor of the mitogen-activated protein kinase cascade. Proc. Natl Acad. Sci. USA 92, 7686–7689 (1995)
Article ADS CAS Google Scholar - Pages, G. et al. Mitogen-activated protein kinases p42mapk and p44mapk are required for fibroblast proliferation. Proc. Natl Acad. Sci. USA 90, 8319–8323 (1993)
Article ADS CAS Google Scholar - Hanafusa, H., Torii, S., Yasunaga, T. & Nishida, E. Sprouty1 and Sprouty2 provide a control mechanism for the Ras/MAPK signalling pathway. Nature Cell Biol. 4, 850–858 (2002)
Article CAS Google Scholar - Casci, T., Vinos, J. & Freeman, M. Sprouty, an intracellular inhibitor of Ras signaling. Cell 96, 655–665 (1999)
Article CAS Google Scholar - Basson, M. A. et al. Sprouty1 is a critical regulator of GDNF/RET-mediated kidney induction. Dev. Cell 8, 229–239 (2005)
Article CAS Google Scholar - Krutzfeldt, J. et al. Silencing of microRNAs in vivo with ‘antagomirs’. Nature 438, 685–689 (2005)
Article ADS Google Scholar - Castoldi, M. et al. A sensitive array for microRNA expression profiling (miChip) based on locked nucleic acids (LNA). RNA 12, 913–920 (2006)
Article CAS Google Scholar - Thum, T. et al. MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure. Circulation 116, 258–267 (2007)
Article CAS Google Scholar - Buitrago, M. et al. The transcriptional repressor Nab1 is a specific regulator of pathological cardiac hypertrophy. Nature Med. 11, 837–844 (2005)
Article CAS Google Scholar - Thum, T. & Borlak, J. Mechanistic role of cytochrome P450 monooxygenases in oxidized low-density lipoprotein-induced vascular injury: therapy through LOX-1 receptor antagonism? Circ. Res. 94, e1–e13 (2004)
Article CAS Google Scholar - Kissler, S. et al. In vivo RNA interference demonstrates a role for Nramp1 in modifying susceptibility to type 1 diabetes. Nature Genet. 38, 479–483 (2006)
Article CAS Google Scholar - Li, X., Wang, W. D. & Lufkin, T. Dicistronic LacZ and alkaline phosphatase reporter constructs permit simultaneous histological analysis of expression from multiple transgenes. Biotechniques 23, 874–878 (1997)
Article CAS Google Scholar - Lewandoski, M., Meyers, E. N. & Martin, G. R. Analysis of Fgf8 gene function in vertebrate development. Cold Spring Harb. Symp. Quant. Biol. 62, 159–168 (1997)
Article CAS Google Scholar - Merkle, S. et al. A role for caspase-1 in heart failure. Circ. Res. 100, 645–653 (2007)
Article CAS Google Scholar
Acknowledgements
We thank N. Hemmrich, U. Keller, J. Schittl, C. Dienesch, S. Thum, A. Leupold, M. Kümmel, S. Schraut, A. Lauer, S. Marquart, E. Leich and A. Horn for technical assistance. We acknowledge the contribution of V. Benes and S. Schmidt (miChip microarray Platform, EMBL), D. Fraccarollo and K. Hu (in vivo studies), S. Leierseder and X. Loyer (primary fibroblast preparation), C. Sohn-Lee (in situ hybridization experiments) and M. Manoharan, R. Braich and B. Bhat (antagomir oligonucleotides). We also thank L. Field, T. Brand and M. Gessler for discussions. This work was supported in part by grants from the IZKF (E-31 to T. Thum), the Deutsche Forschungsgemeinschaft (DFG TH903/7-1 to T. Thum and J.B.), the Rudolf Virchow Center/DFG Research Center for Experimental Biomedicine (S.E., S.K.), the Bavarian Ministry of Technology, ProCorde and Sanofi-Aventis (S.E.), and the US NIH (R01 CA78711 to G.R.M.). M.C. is supported by an Excellence Fellowship of The Medical Faculty of the University of Heidelberg, M.U.M. by a Cancer Research Net grant (BMBF (NGFN) 201GS0450), and M.B. by the Leopoldina Academy (BMBF-LPD 9901/8-141).
Author Contributions T. Thum, C.G., J.F., T.F., S.K., M.B., P.G., S.J., M.C. and S.E. performed experiments. M.A.B and J.D.L. provided the Spry/LacZ mouse line. J.T.R.P., S.H.R. and T. Tuschl contributed the in situ hybridization experiments. T. Thum, C.G., J.F., W.R., S.F., J.S., V.K., A.R., M.M., G.R.M., J.B. and S.E. analysed data. T. Thum, J.B. and S.E. designed the study. T. Thum, G.R.M., J.B. and S.E. wrote the manuscript. J.B. and S.E. contributed equally as joint senior authors to the study.
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Author notes
- Thomas Thum and Carina Gross: These authors contributed equally to this work.
Authors and Affiliations
- Department of Medicine I,,
Thomas Thum, Jan Fiedler, Paolo Galuppo, Stefan Frantz & Johann Bauersachs - Junior Research Group, Interdisziplinäres Zentrum für Klinische Forschung (IZKF),
Thomas Thum & Jan Fiedler - Rudolf Virchow Center, Deutsche Forschungsgemeinschaft (DFG) Research Center for Experimental Biomedicine,,
Carina Gross, Thomas Fischer, Stephan Kissler & Stefan Engelhardt - Institute of Pathology, University of Wuerzburg, 97080 Wuerzburg, Germany ,
Andreas Rosenwald - Department of Anatomy, University of California, San Francisco, California 94158, USA,
Markus Bussen & Gail R. Martin - Department of Internal Medicine III,,
Steffen Just & Wolfgang Rottbauer - Department of Pediatric Hematology, Oncology and Immunology,
Mirco Castoldi & Martina U. Muckenthaler - Molecular Medicine Partnership Unit, University of Heidelberg, 69120 Heidelberg, Germany
Mirco Castoldi & Martina U. Muckenthaler - Regulus Therapeutics, Carlsbad, California 92008, USA ,
Jürgen Soutschek - Alnylam Pharmaceuticals, Cambridge, Massachusetts 02142, USA ,
Victor Koteliansky - Department of Craniofacial Development, King’s College, London SE1 9RT, UK
M. Albert Basson - Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA ,
Jonathan D. Licht - Laboratory of RNA Molecular Biology, Rockefeller University, New York, New York 10065, USA ,
John T. R. Pena, Sara H. Rouhanifard & Thomas Tuschl - Institute of Pharmacology and Toxicology, Technische Universitaet Muenchen (TUM), 80802 Muenchen, Germany
Stefan Engelhardt
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T. Thum, C.G., J.B. and S.E. have submitted a patent application on the use of microRNAs in heart disease.
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Thum, T., Gross, C., Fiedler, J. et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts.Nature 456, 980–984 (2008). https://doi.org/10.1038/nature07511
- Received: 19 January 2008
- Accepted: 03 October 2008
- Published: 30 November 2008
- Issue Date: 18 December 2008
- DOI: https://doi.org/10.1038/nature07511