title: Activation of the hypoxia-inducible factor 1α promotes myogenesis through the noncanonical Wnt pathway, leading to hypertrophic myotubes.
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 an undifferentiated state. Herein we 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.-Cirillo, F., Resmini, G., Ghiroldi, A., Piccoli, M., Bergante, S., Tettamanti, G., Anastasia, L. Activation of the hypoxia-inducible factor 1α promotes myogenesis through the noncanonical Wnt pathway, leading to hypertrophic myotubes.
authors.affiliation: Laboratory of Stem Cells for Tissue Engineering, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Donato, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Cirillo
authors.affiliation: Laboratory of Stem Cells for Tissue Engineering, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Donato, Milan, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Resmini
authors.affiliation: Laboratory of Stem Cells for Tissue Engineering, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Donato, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ghiroldi
authors.affiliation: Laboratory of Stem Cells for Tissue Engineering, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Donato, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Piccoli
authors.affiliation: Laboratory of Stem Cells for Tissue Engineering, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Donato, Milan, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Bergante
authors.affiliation: Laboratory of Stem Cells for Tissue Engineering, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Donato, Milan, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Tettamanti
authors.affiliation: Laboratory of Stem Cells for Tissue Engineering, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Donato, Milan, Italy; luigi.anastasia@unimi.it.|Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Anastasia
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D006984:Hypertrophy / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D051379:Mice; D024510:Muscle Development / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D032448:Myoblasts, Skeletal / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495267:CTNNB1 protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D051176:beta Catenin
keywords: HIF-1α; MyoD; myoblasts; skeletal muscle differentiation