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

Mnatsakanyan, H., Sabateri Serra, R., Rico, P. and Salmerón-Sánchez, M. (2018) Zinc uptake promotes myoblast differentiation via Zip7 transporter and activation of Akt signalling transduction pathway. Scientific Reports, 8, 13642. (doi:10.1038/s41598-018-32067-0) (PMID:30206294)

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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.

Item Type:Articles
Additional Information:P.R. and R.S. acknowledges support from the Spanish Ministry of Economy and Competitiveness (MINECO) (MAT2015-69315-C3-1-R). P.R. acknowledges the Fondo Europeo de Desarrollo Regional (FEDER). CIBER-BBN is an initiative funded by the VI National R&D&I Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. R.S. acknowledges the support from the Spanish MECD through the PRX16/00208 grant.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Salmeron-Sanchez, Professor Manuel
Authors: Mnatsakanyan, H., Sabateri Serra, R., Rico, P., and Salmerón-Sánchez, M.
College/School:College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Scientific Reports
Publisher:Nature Publishing Group
ISSN:2045-2322
ISSN (Online):2045-2322
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Scientific Reports 8:13642
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
626901HEALINSYNERGY - Material-driven fibronectin fibrillogenesis to engineer synergisticgrowth factor microenvironmentsManuel Salmeron-SanchezEuropean Research Council (ERC)306990ENG - BIOMEDICAL ENGINEERING
722061Engineering growth factor microenvironments- a new therapeutic paradigm for regenerative medicineManuel Salmeron-SanchezEngineering and Physical Sciences Research Council (EPSRC)EP/P001114/1ENG - BIOMEDICAL ENGINEERING