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)-1Î± under hypoxia, in murine skeletal myoblasts, leads to activation of MyoD through the noncanonical Wnt/Î²-catenin pathway. Moreover, chemical inhibition of HIF-1Î± 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-1Î±. 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 / F. Cirillo, G. Resmini, A. Ghiroldi, M. Piccoli, S. Bergante, G. Tettamanti, L. Anastasia. - In: THE FASEB JOURNAL. - ISSN 0892-6638. - 31:5(2017 May), pp. 2146-2156.
|Titolo:||Activation of the hypoxia-inducible factor 1a promotes myogenesis through the noncanonical Wnt pathway, leading to hypertrophic myotubes|
RESMINI, GIULIA (Secondo)
TETTAMANTI, GUIDO (Penultimo)
ANASTASIA, LUIGI (Ultimo)
|Parole Chiave:||HIF-1Î±; 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|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
|Data di pubblicazione:||mag-2017|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1096/fj.201600878R|
|Appare nelle tipologie:||01 - Articolo su periodico|