Myofibroblasts protect myoblasts from intrinsic apoptosis associated with differentiation via β1 integrin‐PI3K/Akt pathway

Zhang, Yu; Li, Hai; Lian, Zhengxing; Li, Ning

doi:10.1111/j.1440-169x.2010.01209.x

Cited by 18 publications

(11 citation statements)

References 42 publications

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“…In vivo studies suggest that ablation of fibroblasts leads to depletion of satellite cells, premature satellite cell differentiation, and results in smaller regenerated myofibers (36). In vitro studies have shown that increasing fibroblasts in co-culture also promotes the migration of myoblasts (18) and that fibroblasts protect myoblasts from apoptosis during differentiation, promoting myotube formation (37). This agrees with our current studies showing that the presence of fibroblasts increases myoblast cell numbers and migration.…”

Section: Resultsmentioning

confidence: 99%

A Triple Co-Culture Method to Investigate the Effect of Macrophages and Fibroblasts on Myoblast Proliferation and Migration

Venter

Niesler

2018

BioTechniques

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The communication between nonmyogenic cells, such as macrophages and fibroblasts, and myoblasts is crucial for successful skeletal muscle repair. In vitro co-culture methods can be used to increase our understanding of these cellular interactions; however, current protocols are restricted to two, often physically separate, cell populations. Here, we demonstrate a novel, inexpensive in vitro triple co-culture method that facilitates the co-culture of at least three cell populations with some degree of cell–cell contact. Using this method, we determined the effect of macrophages and fibroblasts on myoblast proliferation and migration. A significant increase in myoblast proliferation and migration was observed following co-culture with either macrophages or fibroblasts. However, triple co-culture of macrophages, fibroblasts, and myoblasts revealed that the presence of macrophages prevented fibroblasts from maintaining this positive effect on myoblast migration. Macrophages, on the other hand, continued to promote myoblast proliferation whether in the presence of fibroblasts or not. Our triple co-culture system highlights the significance of multicellular communication in regulating myoblast proliferation and migration and emphasizes the importance of more complex co-culture systems when investigating myogenesis in vitro.

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Section: Resultsmentioning

confidence: 99%

A Triple Co-Culture Method to Investigate the Effect of Macrophages and Fibroblasts on Myoblast Proliferation and Migration

Venter

Niesler

2018

BioTechniques

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“…Recent evidence has been provided for the control of AKT activity by integrins [48]. Particularly, ILK has been demonstrated to have a strong effect on Ser-473 phosphorylation of AKT [49].…”

Section: Discussionmentioning

confidence: 99%

Phenotype Selection Reveals Coevolution of Muscle Glycogen and Protein and PTEN as a Gate Keeper for the Accretion of Muscle Mass in Adult Female Mice

et al. 2012

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We have investigated molecular mechanisms for muscle mass accretion in a non-inbred mouse model (DU6P mice) characterized by extreme muscle mass. This extreme muscle mass was developed during 138 generations of phenotype selection for high protein content. Due to the repeated trait selection a complex setting of different mechanisms was expected to be enriched during the selection experiment. In muscle from 29-week female DU6P mice we have identified robust increases of protein kinase B activation (AKT, Ser-473, up to 2-fold) if compared to 11- and 54-week DU6P mice or controls. While a number of accepted effectors of AKT activation, including IGF-I, IGF-II, insulin/IGF-receptor, myostatin or integrin-linked kinase (ILK), were not correlated with this increase, phosphatase and tensin homologue deleted on chromosome 10 (PTEN) was down-regulated in 29-week female DU6P mice. In addition, higher levels of PTEN phosphorylation were found identifying a second mechanism of PTEN inhibition. Inhibition of PTEN and activation of AKT correlated with specific activation of p70S6 kinase and ribosomal protein S6, reduced phosphorylation of eukaryotic initiation factor 2α (eIF2α) and higher rates of protein synthesis in 29-week female DU6P mice. On the other hand, AKT activation also translated into specific inactivation of glycogen synthase kinase 3ß (GSK3ß) and an increase of muscular glycogen. In muscles from 29-week female DU6P mice a significant increase of protein/DNA was identified, which was not due to a reduction of protein breakdown or to specific increases of translation initiation. Instead our data support the conclusion that a higher rate of protein translation is contributing to the higher muscle mass in mid-aged female DU6P mice. Our results further reveal coevolution of high protein and high glycogen content during the selection experiment and identify PTEN as gate keeper for muscle mass in mid-aged female DU6P mice.

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“…PIK3R1 and FST are not only target genes of E2F1 (8), but also important members of signal pathways that regulate myogenesis. It has been shown, using C2C12 myoblasts, that the PI3K pathway regulates the myoblast migration (20), proliferation (21,36), differentiation (21,40,53,55,67), and fusion (52), as well as increase of myotube size (28, 48) during myogenesis. PIK3R1 is a subunit of PI3K pathway, affecting muscle development and growth in zebrafish and mouse (37,41).…”

Section: Discussionmentioning

confidence: 99%

Identification of the crucial molecular events during the large-scale myoblast fusion in sheep

Wei

et al. 2014

Physiological Genomics

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It is well known that in sheep most myofibers are formed before birth; however, the crucial myogenic stage and the cellular and molecular mechanisms underpinning phenotypic variation of fetal muscle development remain to be ascertained. We used histological, microarray, and quantitative realtime PCR (qPCR) methods to examine the developmental characteristics of fetal muscle at 70, 85, 100, 120, and 135 days of gestation in sheep. We show that day 100 is an important checkpoint for change in muscle transcriptome and histomorphology in fetal sheep and that the period of 85-100 days is the vital developmental stage for large-scale myoblast fusion. Furthermore, we identified the cisregulatory motifs for E2F1 or MEF2A in a list of decreasingly or increasingly expressed genes between 85 and 100 days, respectively. Further analysis demonstrated that the mRNA and phosphorylated protein levels of E2F1 and MEF2A significantly declined with myogenic progression in vivo and in vitro. qRT-PCR analysis indicated that PI3K and FST, as targets of E2F1, may be involved in myoblast differentiation and fusion and that downregulation of MEF2A contributes to transition of myofiber types by differential regulation of the target genes involved at the stage of 85-100 days. We clarify for the first time the timing of myofiber proliferation and development during gestation in sheep, which would be beneficial to meat sheep production. Our findings present a repertoire of gene expression in muscle during large-scale myoblast fusion at transcriptome-wide level, which contributes to elucidate the regulatory network of myogenic differentiation.sheep; muscle; cis-regulatory motif; histology; microarray UNLIKE THE SMALL MAMMALS with two myogenic waves during development, there are at least three generations of myotubes in sheep (63). Myofiber formation in the sheep fetus begins at ϳ32 days of gestation, and the full complement of myofibers is achieved by days 80 -120 of gestation (3,39). Previous studies provide the valuable information on association between gene expression and prenatal skeletal muscle development in sheep at transcriptome-wide level (10,50,62). However, to our best knowledge, we still do not know the specific developmental stage at which large-scale fetal myoblasts undergo differentiation and fusion in sheep, or the ongoing molecular mechanisms underpinning the phenotypic variations in muscle during the fetal period.Myogenesis is a multiple-step process, including cell determination, proliferation, differentiation, and fusion, that is orchestrated by the expression of a cascade of transcriptional regulators such as Pax3/Pax7, members of the MyoD, MEF2, and E2F family, and so on (9, 44, 59). Myoblast fusion is a critical process that contributes to the growth of muscle during development and to the regeneration of myofibers upon injury. Myoblasts fuse with each other as well as with multinucleated myotubes to enlarge the myofiber. At the cellular level, the fusion process is characterized by the alignment of myoblast and myotu...

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Myofibroblasts protect myoblasts from intrinsic apoptosis associated with differentiation via β1 integrin‐PI3K/Akt pathway

Cited by 18 publications

References 42 publications

A Triple Co-Culture Method to Investigate the Effect of Macrophages and Fibroblasts on Myoblast Proliferation and Migration

A Triple Co-Culture Method to Investigate the Effect of Macrophages and Fibroblasts on Myoblast Proliferation and Migration

Phenotype Selection Reveals Coevolution of Muscle Glycogen and Protein and PTEN as a Gate Keeper for the Accretion of Muscle Mass in Adult Female Mice

Identification of the crucial molecular events during the large-scale myoblast fusion in sheep

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