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.

Activation of the hypoxia-inducible factor 1a promotes myogenesis through the noncanonical Wnt pathway, leading to hypertrophic myotubes / Cirillo, F.; Resmini, G.; Ghiroldi, A.; Piccoli, M.; Bergante, S.; Tettamanti, G.; Anastasia, L.. - In: THE FASEB JOURNAL. - ISSN 0892-6638. - 31:5(2017), pp. 2146-2156. [10.1096/fj.201600878R]

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

L. Anastasia
2017-01-01

Abstract

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.
2017
HIF-1α; Myoblasts; MyoD; Skeletal muscle differentiation; Animals; Cell Differentiation; Cell Line; Hypertrophy; Hypoxia-Inducible Factor 1; alpha Subunit; Mice; Muscle Development; Muscle Fibers; Skeletal; Muscle; Skeletal; Myoblasts; Skeletal; RNA; Messenger; Regeneration; Wnt Signaling Pathway; beta Catenin; Biotechnology; Biochemistry; Molecular Biology; Genetics
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/93259
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