Inhibition of the myostatin/Smad signaling pathway by short decorin-derived peptides

Shafey, Nelly El; Guesnon, Mickaël; Simon, Françoise; Deprez, Eric; Cosette, Jérémie; Stockholm, Daniel; Scherman, Daniel; Bigey, Pascal; Kichler, Antoine

doi:10.1016/j.yexcr.2016.01.019

Cited by 29 publications

(26 citation statements)

References 54 publications

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“…3A). Given that myostatin, another molecule that is involved in muscle atrophy, is counteracted by decorin [25,27,37] and is closely associated with AMPK-mediated energy metabolism and atrophy [38][39][40][41], we evaluated the expression of myostatin in inflamed C2C12 myotubes. We found that the expression levels of myostatin and MAFbx in C2C12 myotubes was significantly increased, while the levels of decorin, MyoD, and myogenin were significantly decreased after treatment with a cytokine mixture for 24 h (Fig.…”

Section: Effects Of Inflammation On Myoblast Differentiation and Myokmentioning

confidence: 99%

“…Therefore, we hypothesized that inflammation alters myokine expression in skeletal muscle cells and that exosomes released from inflammatory muscle cells are responsible for suppressing muscle differentiation. Among myokines, in particular, it has been reported that decorin downregulates the activity of the anti-myogenic myostatin/Smad [25][26][27] and is associated with muscle regeneration [10], hypertrophy [28], and myogenic differentiation [29]. Therefore, we evaluated the effects of inflammation on the expression of decorin and myostatin and on the molecular switches of muscle differentiation using C2C12 myotubes.…”

Section: Introductionmentioning

confidence: 99%

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Roles of Exosome-Like Vesicles Released from Inflammatory C2C12 Myotubes: Regulation of Myocyte Differentiation and Myokine Expression

Kim

Lee

Choi

et al. 2018

Cell Physiol Biochem

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Background/Aims: The complicated differentiation processes of cells in skeletal muscle against inflammation that induce muscle atrophy are not fully elucidated. Given that skeletal muscle is a secretory organ, we evaluated the effects of inflammation on myogenic signals and myokine expression, and the roles of inflammatory exosomes released by myotubes in myogenic differentiation. Methods: Inflammation was induced by treatment of fully differentiated C2C12 myotubes with a cytokine mixture of TNF-α and INF-γ. Exosome-like vesicles (ELVs) were isolated from conditioned media of control or inflamed myotubes and incubated with myoblasts. The expression of molecular switches that contribute to myogenic differentiation, including several kinases, their downstream targets, and myokines, were evaluated using immunoblot analysis in inflamed myotubes and in myoblasts treated with ELVs. Results: Inflammation activated molecular mechanisms contributing to muscle atrophy, including AMPK, p-38 MAPK and JNK, while inhibiting Akt-mediated myogenic signals. In addition, inflammation induced myostatin expression with suppression of a myostatin-counteracting myokine, decorin. Well-characterized ELVs released from inflamed myotubes induced myoblast inflammation and inhibited myogenic mechanisms while stimulating atrophic signals. Conclusion: Inflammation of skeletal muscle induces muscle atrophy via multiple mechanisms, including the regulation of myokines and kinases. Inflammatory ELVs are likely to contribute to inflammation-induced muscle atrophy.

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Section: Effects Of Inflammation On Myoblast Differentiation and Myokmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Roles of Exosome-Like Vesicles Released from Inflammatory C2C12 Myotubes: Regulation of Myocyte Differentiation and Myokine Expression

Kim

Lee

Choi

et al. 2018

Cell Physiol Biochem

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“…In angiogenesis, the effect of decorin is context‐dependent, excluding tumourigenesis where decorin acts as an anti‐oncogenic molecule (Järveläinen et al, ). Furthermore, evidence exists that it has a regulatory role in postpartum cell differentiation, including myotube (El Shafey et al, ) and nephron progenitor cell differentiation (Fetting et al, ) as well as spermatogenesis (Adam et al, ). In myogenesis, decorin activates the differentiation of myogenic cells into skeletal muscle cells via binding and inactivating the mature myostatin in a zinc‐dependent manner (El Shafey et al, ).…”

Section: Decorin – Structure Interactions and Functionsmentioning

confidence: 99%

“…Furthermore, evidence exists that it has a regulatory role in postpartum cell differentiation, including myotube (El Shafey et al, ) and nephron progenitor cell differentiation (Fetting et al, ) as well as spermatogenesis (Adam et al, ). In myogenesis, decorin activates the differentiation of myogenic cells into skeletal muscle cells via binding and inactivating the mature myostatin in a zinc‐dependent manner (El Shafey et al, ). Myostatin is a member of the TGF‐β superfamily, and it is involved in the regulation of skeletal muscle mass.…”

Section: Decorin – Structure Interactions and Functionsmentioning

confidence: 99%

“…In the context of tumourigenesis, the role of decorin is anti‐angiogenic. Studies have demonstrated that also peptides derived from decorin possess anti‐angiogenic properties, similar to the mother molecule (Sulochana et al, ; El Shafey et al, ). For instance, a 26‐residue LRR‐5 peptide was demonstrated to prevent angiogenesis via any different signalling pathways, including inhibition of VEGF‐activated migration of endothelial cells, and cell attachment to fibronectin (Sulochana et al, ).…”

Section: Decorin – Structure Interactions and Functionsmentioning

confidence: 99%

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Decorin‐mediated oncosuppression – a potential future adjuvant therapy for human epithelial cancers

Sainio

Järveläinen

2018

British J Pharmacology

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Currently, the multifaceted role of the extracellular matrix (ECM) in tumourigenesis has been realized. One ECM macromolecule exhibiting potent oncosuppressive actions in tumourigenesis is decorin, the prototype of the small leucine‐rich proteoglycan gene family. The actions of decorin include its ability to function as an endogenous pan‐receptor tyrosine kinase inhibitor, a regulator of both autophagy and mitophagy, as well as a modulator of the immune system. In this review, we will discuss these topics in more detail. We also provide a summary of preclinical studies exploring the value of decorin‐mediated oncosuppression, as a potential future adjuvant therapy for epithelial cancers.Linked ArticlesThis article is part of a themed section on Translating the Matrix. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.1/issuetoc

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Syndecan‐4 influences mammalian myoblast proliferation by modulating myostatin signalling and G1/S transition

et al. 2018

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Myostatin, a TGF‐β superfamily member, is a negative regulator of muscle growth. Here we describe how myostatin activity is regulated by syndecan‐4, a ubiquitous transmembrane heparan sulfate proteoglycan. During muscle regeneration the levels of both syndecan‐4 and promyostatin decline gradually after a sharp increase, concurrently with the release of mature myostatin. Promyostatin and syndecan‐4 co‐immunoprecipitate, and the interaction is heparinase‐sensitive. ShRNA‐mediated silencing of syndecan‐4 reduces C2C12 myoblast proliferation via blocking the progression from G1‐ to S‐phase of the cell cycle, which is accompanied by elevated levels of myostatin and p21(Waf1/Cip1), and decreases in cyclin E and cyclin D1 expression. Our results suggest that syndecan‐4 functions as a reservoir for promyostatin regulating the local bioavailability of mature myostatin.

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Inhibition of the myostatin/Smad signaling pathway by short decorin-derived peptides

Cited by 29 publications

References 54 publications

Roles of Exosome-Like Vesicles Released from Inflammatory C2C12 Myotubes: Regulation of Myocyte Differentiation and Myokine Expression

Roles of Exosome-Like Vesicles Released from Inflammatory C2C12 Myotubes: Regulation of Myocyte Differentiation and Myokine Expression

Decorin‐mediated oncosuppression – a potential future adjuvant therapy for human epithelial cancers

Syndecan‐4 influences mammalian myoblast proliferation by modulating myostatin signalling and G1/S transition

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