Zinc uptake promotes myoblast differentiation via Zip7 transporter and activation of Akt signalling transduction pathway

Sci Rep. 2018 Sep 11;8(1):13642. doi: 10.1038/s41598-018-32067-0.

Abstract

Myogenic regeneration occurs through a chain of events beginning with the output of satellite cells from quiescent state, formation of competent myoblasts and later fusion and differentiation into myofibres. Traditionally, growth factors are used to stimulate muscle regeneration but this involves serious off-target effects, including alterations in cell homeostasis and cancer. In this work, we have studied the use of zinc to trigger myogenic differentiation. We show that zinc promotes myoblast proliferation, differentiation and maturation of myofibres. We demonstrate that this process occurs through the PI3K/Akt pathway, via zinc stimulation of transporter Zip7. Depletion of zinc transporter Zip7 by RNA interference shows reduction of both PI3K/Akt signalling and a significant reduction of multinucleated myofibres and myotubes development. Moreover, we show that mature myofibres, obtained through stimulation with high concentrations of zinc, accumulate zinc and so we hypothesise their function as zinc reservoirs into the cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cation Transport Proteins / genetics*
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics*
  • Cell Proliferation / drug effects
  • Gene Expression Regulation, Developmental / drug effects
  • Mice
  • Muscle Development / drug effects
  • Muscle Development / genetics*
  • Muscle, Skeletal / growth & development
  • Muscle, Skeletal / metabolism
  • Myoblasts / cytology
  • Myoblasts / metabolism
  • Oncogene Protein v-akt / genetics
  • Phosphorylation
  • Regeneration / drug effects
  • Regeneration / genetics*
  • Zinc / pharmacology

Substances

  • Cation Transport Proteins
  • Zip7 protein, mouse
  • Oncogene Protein v-akt
  • Zinc