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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dystrophin / metabolism*
  • Dystrophin / physiology
  • Gene Expression Regulation
  • Histone Deacetylase 2 / metabolism
  • Mice
  • Mice, Inbred mdx
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / physiology
  • Muscular Dystrophy, Animal / enzymology*
  • Nitric Oxide Synthase Type I / metabolism*
  • Regeneration
  • Satellite Cells, Skeletal Muscle / physiology


  • Dystrophin
  • MicroRNAs
  • Nitric Oxide Synthase Type I
  • Hdac2 protein, mouse
  • Histone Deacetylase 2