HIF modulation of Wnt signaling regulates skeletal myogenesis <i>in vivo</i>

Majmundar, Amar J.; Lee, D. S. M.; Skuli, Nicolas; Mesquita, Rickson C.; Kim, M. N.; Yodh, A. G.; Nguyen-McCarty, Michelle; Li, B.; Simon, M. Celeste

doi:10.1242/jcs.177576

Cited by 14 publications

(21 citation statements)

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“…Nonetheless, under the same experimental conditions, we observed the activation of the noncanonical WNT pathway, as confirmed by the up‐regulation of WNT4, WNT7a, and WNT9a, as well as the translocation of β‐catenin to the plasma membrane. Interestingly, a previous study with slightly, yet possibly crucially, different experimental conditions showed that a 0.5% O 2 treatment for 48 h, instead of 24 h, caused a robust down‐regulation of the WNT canonical pathway, which determined the complete inhibition of skeletal muscle differentiation (27). Indeed, when we optimized the pretreatment conditions, we found that subjecting C2C12 cells to hypoxia for more than 24 h caused significant cell death and complete inhibition of the differentiation process, supporting the notion that the effects of sustained hypoxia can vary depending on the treatment length.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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“…In a recent study, Majmundar et al . (58) showed that C2C12 cell differentiation is inhibited by hypoxia (0.5% O 2 ), which is partially prevented by the inhibition of Hif1a. Altogether, it seems that HIF‐1α distinctly regulates myogenesis in standard conditions compared with hypoxic conditions (58, 63).…”

Section: Molecular Mechanisms Underlying Satellite Cell Activity and mentioning

confidence: 99%

“…Majmundar et al . (58) recently explored the role of HIF‐1α in murine skeletal muscle development and skeletal muscle regeneration after ischemic injury. They demonstrated that the deletion of the Hif1a gene specifically in Pax3 + presomitic mesoderm cells (which differentiate in several tissues, including skeletal muscle) did not affect the embryonic and fetal skeletal muscle formation.…”

Section: Molecular Mechanisms Underlying Satellite Cell Activity and mentioning

confidence: 99%

“…To explore the mechanisms behind the HIF‐1α‐induced impairment of regeneration in ischemic muscles, Majmundar et al . (58) exposed C2C12 myoblasts to hypoxia. They revealed that the inhibition of C2C12 myoblast differentiation in hypoxia (0.5% O 2 ) was partially prevented by Hif1a inhibition.…”

Section: Molecular Mechanisms Underlying Satellite Cell Activity and mentioning

confidence: 99%

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Regulation of myogenesis and skeletal muscle regeneration: effects of oxygen levels on satellite cell activity

Chaillou

Lanner

2016

FASEB j.

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Reduced oxygen (O) levels (hypoxia) are present during embryogenesis and exposure to altitude and in pathologic conditions. During embryogenesis, myogenic progenitor cells reside in a hypoxic microenvironment, which may regulate their activity. Satellite cells are myogenic progenitor cells localized in a local environment, suggesting that the O level could affect their activity during muscle regeneration. In this review, we present the idea that O levels regulate myogenesis and muscle regeneration, we elucidate the molecular mechanisms underlying myogenesis and muscle regeneration in hypoxia and depict therapeutic strategies using changes in O levels to promote muscle regeneration. Severe hypoxia (≤1% O) appears detrimental for myogenic differentiation in vitro, whereas a 3-6% O level could promote myogenesis. Hypoxia impairs the regenerative capacity of injured muscles. Although it remains to be explored, hypoxia may contribute to the muscle damage observed in patients with pathologies associated with hypoxia (chronic obstructive pulmonary disease, and peripheral arterial disease). Hypoxia affects satellite cell activity and myogenesis through mechanisms dependent and independent of hypoxia-inducible factor-1α. Finally, hyperbaric oxygen therapy and transplantation of hypoxia-conditioned myoblasts are beneficial procedures to enhance muscle regeneration in animals. These therapies may be clinically relevant to treatment of patients with severe muscle damage.-Chaillou, T. Lanner, J. T. Regulation of myogenesis and skeletal muscle regeneration: effects of oxygen levels on satellite cell activity.

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“…), inhibition of adult progenitor‐dependent myogenesis (Majmundar et al . ), a feature thought to match regeneration with nutrient availability, and enhanced energy recovery in response to ischaemic insults (Niemi et al . ).…”

Section: Introductionmentioning

confidence: 99%

Skeletal muscle hypoxia‐inducible factor‐1 and exercise

Lindholm

Rundqvist

2015

Experimental Physiology

115

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Reduced oxygen levels in skeletal muscle during exercise are a consequence of increased oxygen consumption. The cellular response to hypoxia is conferred to a large extent by activation of the hypoxia-sensitive transcription factor hypoxia-inducible factor-1 (HIF-1). The target genes of HIF-1 increase oxygen transport through mechanisms such as erythropoietin-mediated erythropoiesis and vascular endothelial growth factor-induced angiogenesis and improve tissue function during low oxygen availability through increased expression of glucose transporters and glycolytic enzymes, which makes HIF-1 an interesting candidate as a mediator of skeletal muscle adaptation to endurance training. However, HIF-1 may also inhibit cellular oxygen consumption and mitochondrial oxidative metabolism, features discordant with the phenotype of a trained muscle. Skeletal muscle readily adjusts to altered functional demands. Adaptation of skeletal muscle to long-term aerobic training enables better aerobic performance at higher intensities through improved metabolic capacity and oxygen supply. The components of acute exercise that act as triggers for adaptation are still largely unknown; however, an early hypothesis was that local hypoxia acts as a possible stimulus for exercise adaptation. The hypoxia-sensitive subunit, HIF-1α, is stabilized in skeletal muscle in response to an acute bout of endurance exercise. However, long-term endurance exercise seems to attenuate the acute HIF-1α response. This attenuation is concurrent with an increase in expression of several negative regulators of the HIF system. We propose that the HIF-1α response is blunted in response to long-term exercise training through induction of its negative regulators and that this inhibition enables the enhanced oxidative metabolism that is part of a local physiological response to exercise.

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HIF modulation of Wnt signaling regulates skeletal myogenesis in vivo

Cited by 14 publications

References 1 publication

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

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

Regulation of myogenesis and skeletal muscle regeneration: effects of oxygen levels on satellite cell activity

Skeletal muscle hypoxia‐inducible factor‐1 and exercise

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