Botulinum toxin type A affects the transcriptome of cell cultures derived from muscle biopsies of controls and spastic patients

Simona Zanotti, Dimos Kapetis, Sara Gibertini, Franco Salerno, Emilio Ciusani, Chiara Colombo, Alessandro Gronchi, Lucia Morandi, Renato Mantegazza, Franco Molteni, Marina Mora

Research output: Contribution to journalArticlepeer-review

Abstract

Botulin toxin (BTX) is widely used for treating skeletal muscle spasticity. Experimental reports on BTX treatment were mainly focused on the neuromuscular junction, while relatively little is known about toxin effects on the muscle cell itself. We investigated possible impact of BTX type A on skeletal muscle cell transcriptome by microarray analysis in muscle-derived cell cultures (fibroblasts, myoblasts and myotubes) from controls and spastic patients, and results were then validated at transcript and protein level. BTX-A treatment of control cells induced major changes in the myogenic component of the transcriptome, whereas the same treatment had a negligible effect in the fibrogenic component. BTX-A treatment of cell cultures from spastic patients induced an increased number of genes differentially expressed both in the fibrogenic and myogenic components. Specifically, BTX-A had a major effect on cell cycle-related genes in myoblasts, on muscle contraction-related genes in myotubes, and on extracellular matrix-related genes in fibroblasts from spastic patients. Our findings show that in vitro BTX-A treatment differentially affects transcript expression in muscle cells from spastic patients compared to those from controls suggesting a direct effect of BTX-A on muscle-specific functional pathways.

Original languageEnglish
Pages (from-to)124-136
Number of pages13
JournalToxicology in Vitro
Volume50
DOIs
Publication statusPublished - Aug 1 2018

Keywords

  • Botulinum toxin-A
  • Fibroblasts
  • Microarray
  • Myoblasts
  • Myotubes
  • Spasticity

ASJC Scopus subject areas

  • Toxicology

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