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Activation of the hypoxia‐inducible factor 1a promotes myogenesis through the noncanonical Wnt pathway, leading to hypertrophic myotubes
Author(s) -
Cirillo Federica,
Resmini Giulia,
Ghiroldi Andrea,
Piccoli Marco,
Bergante Sonia,
Tettamanti Guido,
Anastasia Luigi
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201600878r
Subject(s) - myogenesis , myod , microbiology and biotechnology , myocyte , wnt signaling pathway , skeletal muscle , hypoxia (environmental) , biology , chemistry , endocrinology , signal transduction , organic chemistry , oxygen
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. FASEB J. 31, 2146–2156 (2017). www.fasebj.org