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EnglishRegeneration 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 / 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 |
| Autori: | RESMINI, GIULIA (Secondo) TETTAMANTI, GUIDO (Penultimo) ANASTASIA, LUIGI (Ultimo) |
| Parole Chiave: | 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 |
| Settore Scientifico Disciplinare: | Settore BIO/10 - Biochimica |
| Data di pubblicazione: | mag-2017 |
| Rivista: | |
| Tipologia: | Article (author) |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1096/fj.201600878R |
| Appare nelle tipologie: | 01 - Articolo su periodico |
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