scholarly journals Transcriptomic Characterisation of the Molecular Mechanisms Induced by RGMa During Skeletal Muscle Hyperplasia and Hypertrophy

2021 ◽  
Author(s):  
Aline Gonçalves Lio Copola ◽  
Íria Gabriela Dias dos Santos ◽  
Luiz Lehmann Coutinho ◽  
Luiz Eduardo Vieira Del Bem ◽  
Paulo Henrique de Almeida Campos Junior ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Axon Guidance ◽  
Muscle Hypertrophy ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Signalling Pathways ◽  
Axon Guidance Molecule ◽  
Guidance Molecule

Abstract Background: The repulsive guidance molecule a (RGMa) is a GPI-anchor axon guidance molecule first found to play important roles during neuronal development. RGMa expression patterns and signalling pathways via Neogenin and/or as BMP coreceptors indicated that this axon guidance molecule could also be working in other processes and diseases, including during myogenesis. Previous works have consistently shown that RGMa is expressed in skeletal muscle cells and that its overexpression induces both nuclei accretion and hypertrophy in muscle cell lineages. However, the cellular components and molecular mechanisms induced by RGMa during the differentiation of skeletal muscle cells are poorly understood. In this work, the global transcription expression profile of RGMa-treated C2C12 myoblasts during the differentiation stage, obtained by RNA-seq, were reported. Results: RGMa treatment could modulate the expression pattern of 2,195 transcripts in C2C12 skeletal muscle, with 943 upregulated and 1,252 downregulated. Among them, RGMa interfered with the expression of several RNA types, including categories related to the regulation of RNA splicing and degradation. The data also suggested that RGMa hyperplasia effects could be due to their capacity to induce the expression of transcripts related to cell-cell adhesion, while RGMa effects on muscle hypertrophy might be due to (i) the activation of the mTOR-Akt independent axis and (ii) the regulation of the expression of transcripts related to atrophy. Finally, RGMa induced the expression of transcripts that encode skeletal muscle structural proteins and members of the signalling pathways associated with GEF and Rho/Rac, common secondary signals of skeletal muscle hypertrophy, and the canonical pathway of the RGMa/Neogenin signalling. Conclusions: These results provide comprehensive knowledge of skeletal muscle transcript changes and pathways in response to RGMa.

scholarly journals Focal adhesion kinase is required for IGF-I-mediated growth of skeletal muscle cells via a TSC2/mTOR/S6K1-associated pathway

2013 ◽  
Vol 305 (2) ◽  
pp. E183-E193 ◽  
Author(s):  
Hannah Crossland ◽  
Abid A. Kazi ◽  
Charles H. Lang ◽  
James A. Timmons ◽  
Philippe Pierre ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Growth ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Muscle Hypertrophy ◽  
Kinase Activity ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Cell Phenotype ◽  
Igf I

Focal adhesion kinase (FAK) is an attachment complex protein associated with the regulation of muscle mass through as-of-yet unclear mechanisms. We tested whether FAK is functionally important for muscle hypertrophy, with the hypothesis that FAK knockdown (FAK-KD) would impede cell growth associated with a trophic stimulus. C2C12 skeletal muscle cells harboring FAK-targeted (FAK-KD) or scrambled (SCR) shRNA were created using lentiviral transfection techniques. Both FAK-KD and SCR myotubes were incubated for 24 h with IGF-I (10 ng/ml), and additional SCR cells (±IGF-1) were incubated with a FAK kinase inhibitor before assay of cell growth. Muscle protein synthesis (MPS) and putative FAK signaling mechanisms (immunoblotting and coimmunoprecipitation) were assessed. IGF-I-induced increases in myotube width (+41 ± 7% vs. non-IGF-I-treated) and total protein (+44 ± 6%) were, after 24 h, attenuated in FAK-KD cells, whereas MPS was suppressed in FAK-KD vs. SCR after 4 h. These blunted responses were associated with attenuated IGF-I-induced FAK Tyr397 phosphorylation and markedly suppressed phosphorylation of tuberous sclerosis complex 2 (TSC2) and critical downstream mTOR signaling (ribosomal S6 kinase, eIF4F assembly) in FAK shRNA cells (all P < 0.05 vs. IGF-I-treated SCR cells). However, binding of FAK to TSC2 or its phosphatase Shp-2 was not affected by IGF-I or cell phenotype. Finally, FAK-KD-mediated suppression of cell growth was recapitulated by direct inhibition of FAK kinase activity in SCR cells. We conclude that FAK is required for IGF-I-induced muscle hypertrophy, signaling through a TSC2/mTOR/S6K1-dependent pathway via means requiring the kinase activity of FAK but not altered FAK-TSC2 or FAK-Shp-2 binding.

scholarly journals The metabolic and molecular mechanisms of hyperammonaemia‐ and hyperethanolaemia‐induced protein catabolism in skeletal muscle cells

2018 ◽  
Vol 233 (12) ◽  
pp. 9663-9673 ◽  
Author(s):  
Hannah Crossland ◽  
Kenneth Smith ◽  
Philip J. Atherton ◽  
Daniel J. Wilkinson
Keyword(s):  
Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Protein Catabolism

Adenosine isolated from Grifola gargal promotes glucose uptake via PI3K and AMPK signalling pathways in skeletal muscle cells

2017 ◽  
Vol 33 ◽  
pp. 268-277 ◽  
Author(s):  
Yasukiyo Yoshioka ◽  
Etsuko Harada ◽  
Danyao Ge ◽  
Kunio Imai ◽  
Hirotaka Katsuzaki ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Signalling Pathways

scholarly journals Modulation of Myoblast Fusion by Caveolin-3 in Dystrophic Skeletal Muscle Cells: Implications for Duchenne Muscular Dystrophy and Limb-Girdle Muscular Dystrophy-1C

2003 ◽  
Vol 14 (10) ◽  
pp. 4075-4088 ◽  
Author(s):  
Daniela Volonte ◽  
Aaron J. Peoples ◽  
Ferruccio Galbiati
Keyword(s):  
Skeletal Muscle ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Molecular Mechanisms ◽  
Muscle Cells ◽  
Myoblast Fusion ◽  
Limb Girdle Muscular Dystrophy ◽  
Skeletal Muscle Cells ◽  
Fusion Process ◽  
Mild Phenotype

Caveolae are vesicular invaginations of the plasma membrane. Caveolin-3 is the principal structural component of caveolae in skeletal muscle cells in vivo. We have recently generated caveolin-3 transgenic mice and demonstrated that overexpression of wild-type caveolin-3 in skeletal muscle fibers is sufficient to induce a Duchenne-like muscular dystrophy phenotype. In addition, we have shown that caveolin-3 null mice display mild muscle fiber degeneration and T-tubule system abnormalities. These data are consistent with the mild phenotype observed in Limb-girdle muscular dystrophy-1C (LGMD-1C) in humans, characterized by a ∼95% reduction of caveolin-3 expression. Thus, caveolin-3 transgenic and null mice represent valid mouse models to study Duchenne muscular dystrophy (DMD) and LGMD-1C, respectively, in humans. Here, we derived conditionally immortalized precursor skeletal muscle cells from caveolin-3 transgenic and null mice. We show that overexpression of caveolin-3 inhibits myoblast fusion to multinucleated myotubes and lack of caveolin-3 enhances the fusion process. M-cadherin and microtubules have been proposed to mediate the fusion of myoblasts to myotubes. Interestingly, we show that M-cadherin is downregulated in caveolin-3 transgenic cells and upregulated in caveolin-3 null cells. For the first time, variations of M-cadherin expression have been linked to a muscular dystrophy phenotype. In addition, we demonstrate that microtubules are disorganized in caveolin-3 null myotubes, indicating the importance of the cytoskeleton network in mediating the phenotype observed in these cells. Taken together, these results propose caveolin-3 as a key player in myoblast fusion and suggest that defects of the fusion process may represent additional molecular mechanisms underlying the pathogenesis of DMD and LGMD-1C in humans.

scholarly journals Somite subdomains, muscle cell origins, and the four muscle regulatory factor proteins.

1994 ◽  
Vol 127 (1) ◽  
pp. 95-105 ◽  
Author(s):  
T H Smith ◽  
A M Kachinsky ◽  
J B Miller
Keyword(s):  
Skeletal Muscle ◽  
Muscle Cell ◽  
Expression Patterns ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Molecular Pathways ◽  
Regulatory Factor ◽  
Dorsal Cells ◽  
Myod Expression

We show by immunohistology that distinct expression patterns of the four muscle regulatory factor (MRF) proteins identify subdomains of mouse somites. Myf-5 and MyoD are, at specific stages, each expressed in both myotome and dermatome cells. Myf-5 expression is initially restricted to dorsal cells in all somites, as is MyoD expression in neck somites. In trunk somites, however, MyoD is initially expressed in ventral cells. Myogenin and MRF4 are restricted to myotome cells, though the MRF4-expressing cells are initially less widely distributed than the myogenin-expressing cells, which are at all stages found throughout the myotome. All somitic myocytes express one or more MRFs. The transiently distinct expression patterns of the four MRF proteins identify dorsal and ventral subdomains of somites, and suggest that skeletal muscle cells in somites originate at multiple sites and via multiple molecular pathways.

Sign in / Sign up

Export Citation Format

Share Document