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Cell Metab. 2010 Oct 6;12(4):341-351. doi: 10.1016/j.cmet.2010.07.008. Epub 2010 Aug 19.

MicroRNAs involved in molecular circuitries relevant for the Duchenne muscular dystrophy pathogenesis are controlled by the dystrophin/nNOS pathway.

Author information

1
Institute Pasteur Cenci-Bolognetti, Department of Genetics and Molecular Biology and IBPM, "SAPIENZA" University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
2
Department of Histology and Medical Embryology, Interuniversity Institute of Myology, "SAPIENZA" University of Rome, Via A. Scarpa, 14, 00161 Rome, Italy.
3
Telethon Institute of Genetics and Medicine, Via P. Castellino 111, 80131 Napoli, Italy.
4
Institute Pasteur Cenci-Bolognetti, Department of Genetics and Molecular Biology and IBPM, "SAPIENZA" University of Rome, P.le A. Moro 5, 00185 Rome, Italy. Electronic address: irene.bozzoni@uniroma1.it.

Abstract

In Duchenne muscular dystrophy (DMD) the absence of dystrophin at the sarcolemma delocalizes and downregulates nitric oxide synthase (nNOS); this alters S-nitrosylation of HDAC2 and its chromatin association. We show that the differential HDAC2 nitrosylation state in Duchenne versus wild-type conditions deregulates the expression of a specific subset of microRNA genes. Several circuitries controlled by the identified microRNAs, such as the one linking miR-1 to the G6PD enzyme and the redox state of cell, or miR-29 to extracellular proteins and the fibrotic process, explain some of the DMD pathogenetic traits. We also show that, at variance with other myomiRs, miR-206 escapes from the dystrophin-nNOS control being produced in activated satellite cells before dystrophin expression; in these cells, it contributes to muscle regeneration through repression of the satellite specific factor, Pax7. We conclude that the pathway activated by dystrophin/nNOS controls several important circuitries increasing the robustness of the muscle differentiation program.

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PMID:
20727829
DOI:
10.1016/j.cmet.2010.07.008
[Indexed for MEDLINE]
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