scholarly journals Label-Free LC-MS/MS Proteomics Analyses Reveal Proteomic Changes Accompanying MSTN KO in C2C12 Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-14
Author(s):  
Lamei Wang ◽  
Yu Huang ◽  
Xiaolong Wang ◽  
Yulin Chen
Keyword(s):  
Skeletal Muscle ◽  
Immune System ◽  
Energy Metabolism ◽  
Signaling Pathway ◽  
Muscle Development ◽  
C2c12 Cells ◽  
C2c12 Myoblast ◽  
Label Free ◽  
Skeletal Muscle Development ◽  
Mitochondrial Energy Metabolism

Analysis of the proteome of myostatin (MSTN) knockout (KO) mouse C2C12 cells has proven valuable to studies investigating the molecular mechanisms by which MSTN regulates skeletal muscle development. To identify new protein/pathway alterations and candidate biomarkers for skeletal muscle development, we compared proteomic profiles of MSTN KO C2C12 cells (KO) with corresponding wild-type cells (NC) using a label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique. A total of 2637 proteins were identified and quantified in KO cells. Among these proteins, 77 proteins were significantly differentially expressed, 38 upregulated, and 39 downregulated, in MSTN KO C2C12 cells. These significantly altered proteins are involved in metabolic processes, developmental processes, immune system processes, and the regulation of other biological processes. Enrichment analysis was utilized to link these alterations to biological pathways, which are predominantly related to oxidative phosphorylation, protein digestion and absorption, mitochondrion localisation, antigen processing and presentation, the MAPK signaling pathway, the PPAR signaling pathway, the PI3K-Akt signaling pathway, and the JAK-STAT signaling pathway. Upregulation of several proteins, including epoxide hydrolase, tropomyosin 1, Cyb5a, HTRA1, Cox6a1, CD109, Synap29, and Ugt1a6, likely enhanced skeletal muscle development, the immune system, and energy metabolism. Collectively, our results present a comprehensive proteomics analysis of MSTN KO C2C12 myoblast cells; we hypothesize that MSTN KO could activate p38MAPK signaling pathway by CDC42, and we further deciphered the function of MSTN in the regulation of skeletal muscle development, immune processes, and mitochondrial energy metabolism.

scholarly journals Myoferlin Regulates Wnt/β-Catenin Signaling-Mediated Skeletal Muscle Development by Stabilizing Dishevelled-2 Against Autophagy

2019 ◽  
Vol 20 (20) ◽  
pp. 5130 ◽  
Author(s):  
Shunshun Han ◽  
Can Cui ◽  
Haorong He ◽  
Xiaoxu Shen ◽  
Yuqi Chen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Muscle Development ◽  
Skeletal Muscle Atrophy ◽  
Myoblast Differentiation ◽  
C2c12 Myoblast ◽  
Skeletal Muscle Development ◽  
Muscle Tissues ◽  
Underlying Mechanisms ◽  
Canonical Wnt

Myoferlin (MyoF), which is a calcium/phospholipid-binding protein expressed in cardiac and muscle tissues, belongs to the ferlin family. While MyoF promotes myoblast differentiation, the underlying mechanisms remain poorly understood. Here, we found that MyoF not only promotes C2C12 myoblast differentiation, but also inhibits muscle atrophy and autophagy. In the present study, we found that myoblasts fail to develop into mature myotubes due to defective differentiation in the absence of MyoF. Meanwhile, MyoF regulates the expression of atrophy-related genes (Atrogin-1 and MuRF1) to rescue muscle atrophy. Furthermore, MyoF interacts with Dishevelled-2 (Dvl-2) to activate canonical Wnt signaling. MyoF facilitates Dvl-2 ubiquitination resistance by reducing LC3-labeled Dvl-2 levels and antagonizing the autophagy system. In conclusion, we found that MyoF plays an important role in myoblast differentiation during skeletal muscle atrophy. At the molecular level, MyoF protects Dvl-2 against autophagy-mediated degradation, thus promoting activation of the Wnt/β-catenin signaling pathway. Together, our findings suggest that MyoF, through stabilizing Dvl-2 and preventing autophagy, regulates Wnt/β-catenin signaling-mediated skeletal muscle development.

scholarly journals Inhibition of the JNK/MAPK signaling pathway by myogenesis-associated miRNAs is required for skeletal muscle development

2018 ◽  
Vol 25 (9) ◽  
pp. 1581-1597 ◽  
Author(s):  
Shu-Juan Xie ◽  
Jun-Hao Li ◽  
Hua-Feng Chen ◽  
Ye-Ya Tan ◽  
Shu-Rong Liu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathway ◽  
Muscle Development ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Skeletal Muscle Development

scholarly journals IGF-II transcription in skeletal myogenesis is controlled by mTOR and nutrients

2003 ◽  
Vol 163 (5) ◽  
pp. 931-936 ◽  
Author(s):  
Ebru Erbay ◽  
In-Hyun Park ◽  
Paul D. Nuzzi ◽  
Christopher J. Schoenherr ◽  
Jie Chen
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Kinase Activity ◽  
Regulatory Elements ◽  
Myoblast Differentiation ◽  
Akt Pathway ◽  
C2c12 Myoblast ◽  
Skeletal Muscle Development ◽  
Primary Target ◽  
Insulin Like Growth Factors

Insulin-like growth factors (IGFs) are essential for skeletal muscle development, regeneration, and hypertrophy. Although autocrine actions of IGF-II are known to initiate myoblast differentiation, the regulatory elements and upstream signaling pathways for myogenic expression of IGF-II remain elusive. Here, we report the regulation of IGF-II transcription by mTOR, as well as by amino acid sufficiency, through the IGF-II promoter 3 and a downstream enhancer during C2C12 myoblast differentiation. Furthermore, we present evidence that IGF production, and not IGF signaling, is the primary target for mTOR's function in the initiation of differentiation. Moreover, myogenic signaling by mTOR is independent of its kinase activity and mediated by the PI3K–Akt pathway. Our findings represent the first identification of a signaling pathway that regulates IGF-II expression in myogenesis and implicate the mTOR–IGF axis as a molecular link between nutritional levels and skeletal muscle development.

scholarly journals Identification of CXCL11 as part of chemokine network controlling skeletal muscle development

2021 ◽  
Author(s):  
Malte Puchert ◽  
Christian Koch ◽  
Konstanze Zieger ◽  
Jürgen Engele
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
C2c12 Cell ◽  
C2c12 Cells ◽  
Muscle Fibres ◽  
Skeletal Muscle Development ◽  
Functional Studies ◽  
Adult Rat ◽  
Limb Muscles ◽  
Chemokine Cxcl12

AbstractThe chemokine, CXCL12, and its receptors, CXCR4 and CXCR7, play pivotal roles during development and maintenance of limb muscles. CXCR7 additionally binds CXCL11, which uses CXCR3 as its prime receptor. Based on this cross-talk, we investigate whether CXCL11 would likewise affect development and/or function of skeletal muscles. Western blotting and immunolabelling demonstrated the developmentally restricted expression of CXCL11 in rat limb muscles, which was contrasted by the continuous expression of its receptors in proliferating and differentiating C2C12 cells as well as in late embryonic to adult rat limb muscle fibres. Consistent with a prime role in muscle formation, functional studies identified CXCL11 as a potent chemoattractant for undifferentiated C2C12 cells and further showed that CXCL11 does neither affect myoblast proliferation and differentiation nor metabolic/catabolic pathways in formed myotubes. The use of selective receptor antagonists unravelled complementary effects of CXCL11 and CXCL12 on C2C12 cell migration, which either require CXCR3/CXCR7 or CXCR4, respectively. Our findings provide new insights into the chemokine network controlling skeletal muscle development and function and, thus, might provide a base for future therapies of muscular diseases.

Regulation of sarcoplasmic reticulum gene expression during cardiac and skeletal muscle development

1992 ◽  
Vol 262 (3) ◽  
pp. C614-C620 ◽  
Author(s):  
M. Arai ◽  
K. Otsu ◽  
D. H. MacLennan ◽  
M. Periasamy
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Cardiac Muscle ◽  
Muscle Development ◽  
C2c12 Cells ◽  
Contractile Protein ◽  
Skeletal Muscle Development ◽  
Slow Twitch ◽  
Nuclease Mapping ◽  
Fast Twitch

The expression of major sarcoplasmic reticulum proteins during cardiac and fast-twitch skeletal muscle development was examined using gene-specific probes. Through the use of S1 nuclease mapping, Northern blot, and RNA slot-blot analysis, sarcoplasmic reticulum proteins were shown to exhibit both narrow tissue specificity and plasticity in their expression during muscle development. In fast-twitch skeletal muscle, the cardiac/slow-twitch isoforms of Ca(2+)-ATPase and calsequestrin were detected at high levels in fetal stages but were gradually replaced by fast-twitch isoforms in adult muscle. In contrast, cardiac muscle expressed exclusively cardiac/slow-twitch isoforms of Ca(2+)-ATPase and calsequestrin at all stages. Both fast-twitch and slow-twitch skeletal muscle expressed the same skeletal muscle ryanodine receptor isoform, whereas cardiac muscle expressed a cardiac isoform. Phospholamban expression was restricted to cardiac and slow-twitch skeletal muscle and did not appear in developing fast-twitch skeletal muscle. During in vitro myogenesis of C2C12 cells, the mRNA transcripts encoding sarcoplasmic reticulum proteins were found to be coordinately induced in synchrony with that of contractile protein mRNA. The myogenic factor "myogenin" induced sarcoplasmic reticulum gene transcripts along with contractile protein mRNAs in nonmyogenic cells. These data suggest that the induction of both sarcoplasmic reticulum and contractile protein gene families is under the control of a common myogenic differentiation program.

scholarly journals Analysis of long intergenic non-coding RNAs transcriptomic profiling in skeletal muscle growth during porcine embryonic development

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wenjuan Zhao ◽  
Zijing Li ◽  
Quan Liu ◽  
Su Xie ◽  
Mengxun Li ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathway ◽  
Muscle Development ◽  
Target Genes ◽  
Muscle Growth ◽  
Skeletal Muscle Development ◽  
Protein Coding ◽  
Development Stages ◽  
Non Coding Rnas ◽  
Embryonic Muscle

AbstractSkeletal muscle growth plays a critical role during porcine muscle development stages. Genome-wide transcriptome analysis reveals that long intergenic non-coding RNAs (lincRNAs) are implicated as crucial regulator involving in epigenetic regulation. However, comprehensive analysis of lincRNAs in embryonic muscle development stages remain still elusive. Here, we investigated the transcriptome profiles of Duroc embryonic muscle tissues from days 33, 65, and 90 of gestation using RNA-seq, and 228 putative lincRNAs were identified. Moreover, these lincRNAs exhibit the characteristics of shorter transcripts length, longer exons, less exon numbers and lower expression level compared with protein-coding transcripts. Expression profile analysis showed that a total of 120 lincRNAs and 2638 mRNAs were differentially expressed. In addition, we also performed quantitative trait locus (QTL) mapping analysis for differentially expressed lincRNAs (DE lincRNAs), 113 of 120 DE lincRNAs were localized on 2200 QTLs, we observed many QTLs involved in growth and meat quality traits. Furthermore, we predicted potential target genes of DE lincRNAs in cis or trans regulation. Gene ontology and pathway analysis reveals that potential targets of DE lincRNAs mostly were enriched in the processes and pathways related to tissue development, MAPK signaling pathway, Wnt signaling pathway, TGF-beta signaling pathway and insulin signaling pathway, which involved in skeletal muscle physiological functions. Based on cluster analysis, co-expression network analysis of DE lincRNAs and their potential target genes indicated that DE lincRNAs highly regulated protein-coding genes associated with skeletal muscle development. In this study, many of the DE lincRNAs may play essential roles in pig muscle growth and muscle mass. Our study provides crucial information for further exploring the molecular mechanisms of lincRNAs during skeletal muscle development.

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