Interleukin-4 improves the migration of human myogenic precursor cells in vitro and in vivo

Lafrenière, Jean-François; Mills, Philippe; Bouchentouf, Manaf; Tremblay, Jacques P.

doi:10.1016/j.yexcr.2006.01.002

Cited by 78 publications

(55 citation statements)

References 57 publications

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“…Since no induction of IL-4 expression was detected following IGF-1 treatment in human myotube cultures, we propose that IL-4 and IL-13 could share the redundant ability to recruit mononucleated cells for fusion but not toward the same cell populations: IL-4 being responsible for the 'normal' myoblast fusion into nascent myotubes during myogenic differentiation, and IL-13 for additional recruitment of reserve cells during IGF-1-induced hypertrophy. This hypothesis was reinforced by the fact that exogenous treatment by IL-13 at the time of differentiation induction induces the same increase in fusion index as when it was added after 3 days of differentiation (data not shown); on the contrary, we observed that IL-4 did not induce any change in the final fusion index when added either at the time of differentiation induction (data not shown) or after 3 days of differentiation, in accordance with previous studies on human and mice myoblasts (Horsley et al, 2003;Lafreniere et al, 2006).We also tested the involvement of IL-15 as a candidate for the activation of reserve cells, since it has been shown to be involved in myotube hypertrophy in mouse, bovine and human myoblasts (Quinn et al, 2002). Although we were able to confirm the expression of IL-15 in human myotubes, we did not observe any increase in IL-15 expression following IGF-1 treatment.…”

supporting

confidence: 93%

IL-13 mediates the recruitment of reserve cells for fusion during IGF-1-induced hypertrophy of human myotubes

Jacquemin

Butler-Browne

Furling

et al. 2007

Journal of Cell Science

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Insulin-like growth factor-1 (IGF-1) has been shown to induce skeletal muscle hypertrophy, to prevent the loss of muscle mass with ageing and to improve the muscle phenotype of dystrophic mice. We previously developed a model of IGF-1-induced hypertrophy of human myotubes, in which hypertrophy was not only characterized by an increase in myotube size and myosin content but also by an increased recruitment of reserve cells for fusion. Here, we describe a new mechanism of IGF-1-induced hypertrophy by demonstrating that IGF-1 signals exclusively to myotubes but not to reserve cells, leading, under the control of the transcription factor NFATc2, to the secretion of IL-13 that will secondly recruit reserve cells for differentiation and fusion. In addition, we show that IGF-1 also signals to myotubes to stimulate protein metabolism via Akt by (1) activating the mTOR-p70S6K-S6 pathway and inhibiting GSK-3␤, both involved in the control of protein translation, and (2) inhibiting the Foxo1-atrogin-1 protein degradation pathway. Journal of Cell Science 671 IL-13-mediated reserve cell recruitment (Abbott et al., 1998;Horsley et al., 2001), the data in the literature concerning the role of calcineurin in skeletal muscle hypertrophy are again often contradictory since some studies in rodent models show that IGF-1-induced hypertrophy can be suppressed using the calcineurin inhibitors cyclosporine A or FK506 Semsarian et al., 1999b), whereas other groups see no effect of these inhibitors on hypertrophy and no increase in calcineurin activity in the presence of IGF-1 (Bodine et al., 2001b;Rommel et al., 2001).The ability of IGF-1 to act as an anabolic factor on skeletal muscle and to counterbalance the signalling pathways of muscle atrophy has led to the proposition that IGF-1 could be used as a therapeutic agent to combat muscle atrophy related to age (sarcopenia) or to various diseases. However all data available until now describing the mechanisms of IGF-1-induced hypertrophy have been obtained in rodent models, and very little is known about the effects and the signalling pathways of IGF-1 in human skeletal muscle. It is becoming increasingly evident that the results obtained in rodent models cannot always be directly transposed to man. For example, whereas a twofold increase was observed in the lifespan of myoblasts from transgenic mice overexpressing IGF-1 in muscle (Chakravarthy et al., 2000), we recently showed in human myoblasts that IGF-1 has no effect on the proliferative lifespan, suggesting a different mechanism of regulation in these two species (Jacquemin et al., 2004).We previously developed an in vitro model of human myotube hypertrophy induced by IGF-1 where cultures were exposed to IGF-1 only 3 days after the induction of differentiation, a time when most of the myoblasts have already fused into myotubes and no more proliferation is observed. This model allows us to distinguish between the different effects of IGF-1 on proliferation, differentiation and hypertrophy (Jacquemin et al., 2004). In these condition...

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supporting

confidence: 93%

IL-13 mediates the recruitment of reserve cells for fusion during IGF-1-induced hypertrophy of human myotubes

Jacquemin

Butler-Browne

Furling

et al. 2007

Journal of Cell Science

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“…The paradoxical effects of IL-4 on rhabdomyosarcoma could be reconciled with the physiologic activities of IL-4 by taking into consideration recent results showing that IL-4 is not required for fusion between mononuclear myoblasts, but for myotube maturation and also for myoblast migration (30). Therefore, IL-4 fosters normal myogenesis by stimulating the movement of precursors towards pre-existing myotubes and favoring myotube accretion through fusion with incoming myoblasts.…”

Section: Discussionmentioning

confidence: 97%

Opposing control of rhabdomyosarcoma growth and differentiation by myogenin and interleukin 4

Nanni

Nicoletti

Palladini

et al. 2009

Molecular Cancer Therapeutics

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Rhabdomyosarcoma is a tumor of striated muscle origin that displays defective myogenic differentiation. Terminal myogenesis switches off cell proliferation and migration, hence, the promotion of rhabdomyosarcoma differentiation should antagonize tumor growth and metastasis. Terminal myogenesis is controlled by cell-intrinsic myogenic transcription factors like myogenin and environmental mediators like interleukin 4 (IL-4). We studied whether the expression of myogenin or exposure to IL-4 could promote the myogenesis of poorly differentiating human rhabdomyosarcoma cells RD/12. Forced expression of myogenin amplified myosin expression and the formation of myotube-like elements, inhibited cell migration, and reduced the growth of local tumors and liver metastases in immunodepressed mice. In contrast, exposure to IL-4 promoted cell proliferation and survival, especially at high cell density, inhibited myogenin expression, and myogenesis. Moreover, IL-4 stimulated the directed migration of cells with low myogenin levels, but not of cells with higher (spontaneous or forced) levels. Thus, IL-4, which was known to promote late stages of normal myogenesis, favors growth and migration, and inhibits further differentiation of the myogenic stages attained by rhabdomyosarcoma cells. Strategies to increase myogenin expression and block IL-4 could simultaneously reduce growth and migration, and enhance terminal differentiation of rhabdomyosarcoma, thus contributing to the control of tumor growth and metastatic spread. [Mol Cancer Ther 2009;8(4):754-61]

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“…Some factors modulate the velocity or direction of cell migration, whereas others regulate the clearance of the extracellular matrix at the leading edge of migrating cells, thereby enhancing cell motility (Horsley et al, 2003;Jansen and Pavlath, 2006;Lafreniere et al, 2006;Griffin et al, 2009). Myoblast fusion in vitro is enhanced by both positive regulators [e.g.…”

Section: Myoblast Migration Recognition and Adhesion In Micementioning

confidence: 99%

“…Myoblast fusion in vitro is enhanced by both positive regulators [e.g. CD164 (Bae et al, 2008), interleukin 4 (Il4) (Horsley et al, 2003;Lafreniere et al, 2006), mannose receptor (MR) (Jansen and Pavlath, 2006) and mouse odorant receptor 23 (Mor23; Olfr16 -Mouse Genome Informatics) (Griffin et al, 2009)] and negative regulators [e.g. prostacyclin (Bondesen et al, 2007)] of cell migration.…”

Section: Myoblast Migration Recognition and Adhesion In Micementioning

confidence: 99%

Myoblast fusion: lessons from flies and mice

2012

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The fusion of myoblasts into multinucleate syncytia plays a fundamental role in muscle function, as it supports the formation of extended sarcomeric arrays, or myofibrils, within a large volume of cytoplasm. Principles learned from the study of myoblast fusion not only enhance our understanding of myogenesis, but also contribute to our perspectives on membrane fusion and cell-cell fusion in a wide array of model organisms and experimental systems. Recent studies have advanced our views of the cell biological processes and crucial proteins that drive myoblast fusion. Here, we provide an overview of myoblast fusion in three model systems that have contributed much to our understanding of these events: the Drosophila embryo; developing and regenerating mouse muscle; and cultured rodent muscle cells. IntroductionThe process of fusing two adjacent membranes accomplishes many goals that are crucial to the development and maintenance of living organisms. Broadly, membrane fusion can occur intracellularly, as with synaptic vesicles, or between cells, as for sperm-egg fusion. Cell fusion occurs in a broad range of organisms, including Saccharomyces cerevisiae and Caenorhabditis elegans, and between several cell types, such as macrophages, placental trophoblasts and myoblasts. Experimental analysis of fusion in these systems has revealed the involvement of a diverse array of specialized molecules.Myoblast fusion, a fundamental step in the differentiation of muscle in most organisms, can involve tens of thousands of myoblasts, Given the complexity of the musculature, fusion must be a regulated process in which the appropriate number of cells fuse at the appropriate time and place. Often these cells migrate long distances prior to fusion, and fusion can involve multiple cell types, necessitating cell recognition and adhesion, which are crucial to accurate and efficient fusion. In addition to the early fusion events that occur during embryogenesis, vertebrate muscle tissue is able to regenerate in response to damage and disease. This regeneration involves proliferation of muscle satellite cells (see Glossary, Box 1) and their subsequent fusion to repair the damaged muscles. The focus of this review is the process of myoblast fusion, which involves cell migration, adhesion and signaling transduction pathways leading up to the actual fusion event. We review the crucial role of the actin cytoskeleton and actin polymerizing proteins, and recently revealed membrane protrusions that may drive fusion itself. We describe three powerful systems for this analysis: Drosophila embryogenesis; mouse embryogenesis and regeneration; and rodent tissue culture. We highlight the genes and morphological events involved in myoblast fusion, as revealed by each system. With the emergence of Danio rerio as another model for myoblast fusion, we also list relevant homologs in this system (Tables 1, 2). Experimental systems for the analysis of myoblast fusionThe ability to isolate and propagate mammalian myoblasts that could differentiate and fuse in...

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Interleukin-4 improves the migration of human myogenic precursor cells in vitro and in vivo

Cited by 78 publications

References 57 publications

IL-13 mediates the recruitment of reserve cells for fusion during IGF-1-induced hypertrophy of human myotubes

IL-13 mediates the recruitment of reserve cells for fusion during IGF-1-induced hypertrophy of human myotubes

Opposing control of rhabdomyosarcoma growth and differentiation by myogenin and interleukin 4

Myoblast fusion: lessons from flies and mice

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