Role of miR-200c in Myogenic Differentiation Impairment via p66Shc: Implication in Skeletal Muscle Regeneration of Dystrophic mdx Mice

  • D’Agostino M
  • Torcinaro A
  • Madaro L
  • et al.
N/ACitations
Citations of this article
5Readers
Mendeley users who have this article in their library.

Abstract

Duchenne muscular dystrophy (DMD) is a genetic disease associated with mutations of Dystrophin gene that regulate myofiber integrity and muscle degeneration, characterized by oxidative stress increase. We previously published that reactive oxygen species (ROS) induce miR-200c that is responsible for apoptosis and senescence. Moreover, we demonstrated that miR-200c increases ROS production and phosphorylates p66Shc in Ser-36. p66Shc plays an important role in muscle differentiation; we previously showed that p66Shc −/− muscle satellite cells display lower oxidative stress levels and higher proliferation rate and differentiated faster than wild-type ( wt ) cells. Moreover, myogenic conversion, induced by MyoD overexpression, is more efficient in p66Shc −/− fibroblasts compared to wt cells. Herein, we report that miR-200c overexpression in cultured myoblasts impairs skeletal muscle differentiation. Further, its overexpression in differentiated myotubes decreases differentiation indexes. Moreover, anti-miR-200c treatment ameliorates myogenic differentiation. In keeping, we found that miR-200c and p66Shc Ser-36 phosphorylation increase in mdx muscles. In conclusion, miR-200c inhibits muscle differentiation, whereas its inhibition ameliorates differentiation and its expression levels are increased in mdx mice and in differentiated human myoblasts of DMD. Therefore, miR-200c might be responsible for muscle wasting and myotube loss, most probably via a p66Shc-dependent mechanism in a pathological disease such as DMD.

Cite

CITATION STYLE

APA

D’Agostino, M., Torcinaro, A., Madaro, L., Marchetti, L., Sileno, S., Beji, S., … Magenta, A. (2018). Role of miR-200c in Myogenic Differentiation Impairment via p66Shc: Implication in Skeletal Muscle Regeneration of Dystrophic mdx Mice . Oxidative Medicine and Cellular Longevity, 2018, 1–10. https://doi.org/10.1155/2018/4814696

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free