Activation of the hypoxia-inducible factor 1a promotes myogenesis through the noncanonical Wnt pathway, leading to hypertrophic myotubes

Federica Cirillo, Giulia Resmini, Andrea Ghiroldi, Marco Piccoli, Sonia Bergante, Guido Tettamanti, Luigi Anastasia, Luigi Anastasia

Research output: Contribution to journalArticlepeer-review

Abstract

© FASEB. Regeneration of skeletal muscle is a complex process that requires the activation of quiescent adult stem cells, called satellite cells, which are resident in hypoxic niches in the tissue. Hypoxia has been recognized as a key factor to maintain stem cells in anundifferentiated state. Hereinwe report that hypoxia plays a fundamental role also in activating myogenesis. In particular, we found that the activation of the hypoxia-inducible factor (HIF)-1α under hypoxia, in murine skeletal myoblasts, leads to activation of MyoD through the noncanonical Wnt/β-catenin pathway. Moreover, chemical inhibition of HIF-1α activity significantly reduces differentiation, thus confirming its crucial role in the process. Furthermore, hypoxia-preconditioned myoblasts, once induced to differentiate under normoxic conditions, tend to form hypertrophic myotubes. These results support the notion that hypoxia plays a pivotal role in activating the regeneration process by directly inducing myogenesis through HIF-1α. Although preliminary, these findings may suggest new perspective for novel therapeutic targets in the treatment of several muscle diseases.
Original languageEnglish
Pages (from-to)2146-2156
Number of pages11
JournalFASEB Journal
Volume31
Issue number5
DOIs
Publication statusPublished - May 1 2017

Keywords

  • HIF-1α
  • Myoblasts
  • MyoD
  • Skeletal muscle differentiation

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