scholarly journals Exogenous Expression of an Alternative Splicing Variant of Myostatin Prompts Leg Muscle Fiber Hyperplasia in Japanese Quail

2019 ◽  
Vol 20 (18) ◽  
pp. 4617 ◽  
Author(s):  
Paula Renee Chen ◽  
Yeunsu Suh ◽  
Sangsu Shin ◽  
Rachel Marie Woodfint ◽  
Seongsoo Hwang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Alternative Splicing ◽  
Japanese Quail ◽  
Muscle Development ◽  
Pectoralis Major Muscle ◽  
Muscle Growth ◽  
Cross Sectional ◽  
Proliferation And Differentiation

Myostatin (MSTN) negatively regulates muscle growth and development through inhibiting myoblast proliferation and differentiation. Five alternative splicing isoforms of MSTN (MSTN-A to MSTN-E) have been discovered in domestic avian species. MSTN-A has high expression in skeletal muscle and encodes the full-length peptide with anti-myogenic activity. Another isoform, MSTN-B, is also highly expressed in skeletal muscle and encodes a truncated peptide that has pro-myogenic capabilities in vitro, which include promoting the proliferation and differentiation of quail muscle precursor cells. The objective of this study was to investigate overexpression of MSTN-B in vivo by using two independent lines of transgenic Japanese quail with expression directed in the skeletal muscle. Unexpectedly, the chicken skeletal muscle alpha actin 1 (cACTA1) promoter resulted in restricted exogenous MSTN-B protein expression to certain skeletal muscles, such as the gastrocnemius and tibialis anterior, but not the pectoralis major muscle. Gastrocnemius weight as a percentage of body weight in transgenic quail was increased compared to non-transgenic quail at posthatch day 21 (D21) and posthatch D42. An increase in the size of the gastrocnemius in transgenic quail was attributed to an increase in fiber number but not fiber cross-sectional area (CSA). During embryonic development, paired box 7 (PAX7) expression was prolonged in the transgenic embryos, but other myogenic regulatory factors (MRFs) were unchanged after MSTN-B overexpression. Taken together, these data provide novel insights into the regulation of skeletal muscle development by alternative splicing mechanisms in avians.

scholarly journals Streptozotocin induces G2 arrest in skeletal muscle myoblasts and impairs muscle growth in vivo

2007 ◽  
Vol 292 (3) ◽  
pp. C1033-C1040 ◽  
Author(s):  
Adam P. W. Johnston ◽  
Jonathan E. Campbell ◽  
Jeremy G. Found ◽  
Michael C. Riddell ◽  
Thomas J. Hawke
Keyword(s):  
Skeletal Muscle ◽  
Muscle Growth ◽  
Phase Cell ◽  
Saline Control ◽  
Dependent Manner ◽  
Β Cell ◽  
Cross Sectional ◽  
M Phase

Streptozotocin (STZ) is used extensively to induce pancreatic β-cell death and ultimately diabetes mellitus in animal models. However, the direct effects of STZ on muscle are largely unknown. To delineate the effects of STZ from the effects of hypoinsulinemia/hyperglycemia, we injected young rats with 1) saline (control), 2) STZ (120 mg/kg) or 3) STZ and insulin (STZ-INS; to maintain euglycemia). STZ rats demonstrated significantly elevated blood glucose throughout the 48-h protocol, while control and STZ-INS rats were euglycemic. Body mass increased in control (13 ± 4 g), decreased by 19 ± 2 g in STZ and remained unchanged in STZ-INS rats (−0.3 ± 2 g). Cross-sectional areas of gastrocnemius muscle fibers were smaller in STZ vs. control (1,480 ± 149 vs. 1,870 ± 40 μm2, respectively; P < 0.05) and insulin treatment did not rescue this defect (STZ-INS: 1,476 ± 143 μm2). Western blot analysis revealed a detectable increase in ubiquitinated proteins in the STZ skeletal muscles compared with control and STZ-INS. To further define the effects of STZ on skeletal muscle, independent of hyperglycemia, myoblasts were exposed to varying doses of STZ (0.25–3.0mg/ml) in vitro. Both acute and chronic exposures of STZ significantly impaired proliferative capacity in a dose-dependent manner. Within STZ-treated myoblasts, increased reactive oxygen species was associated with significant G2/M phase cell-cycle arrest. Taken together, our findings show that the effects of STZ are not β-cell specific and reveal that STZ should not be used for studies examining diabetic myopathy.

scholarly journals Androgens induce growth of the limb skeletal muscles in a rapamycin-insensitive manner

2018 ◽  
Vol 315 (4) ◽  
pp. R721-R729 ◽  
Author(s):  
Michael L. Rossetti ◽  
David H. Fukuda ◽  
Bradley S. Gordon
Keyword(s):  
Skeletal Muscle ◽  
Fiber Type ◽  
Muscle Growth ◽  
Total Protein Content ◽  
Cross Sectional ◽  
S6 Kinase ◽  
Mechanistic Target Of Rapamycin ◽  
Ribosomal S6 Kinase

Signaling through the mechanistic target of rapamycin complex 1 (mTORC1) has been well defined as an androgen-sensitive transducer mediating skeletal muscle growth in vitro; however, this has yet to be tested in vivo. As such, male mice were subjected to either sham or castration surgery and allowed to recover for 7 wk to induce atrophy of skeletal muscle. Then, castrated mice were implanted with either a control pellet or a pellet that administered rapamycin (~2.5 mg·kg−1·day−1). Seven days postimplant, a subset of castrated mice with control pellets and all castrated mice with rapamycin pellets were given once weekly injections of nandrolone decanoate (ND) to induce muscle growth over a six-week period. Effective blockade of mTORC1 by rapamycin was noted in the skeletal muscle by the inability of insulin to induce phosphorylation of ribosomal S6 kinase 1 70 kDa (Thr389) and uncoordinated-like kinase 1 (Ser757). While castration reduced tibialis anterior (TA) mass, muscle fiber cross-sectional area, and total protein content, ND administration restored these measures to sham levels in a rapamycin-insensitive manner. Similar findings were also observed in the plantaris and soleus, suggesting this rapamycin-insensitive effect was not specific to the TA or fiber type. Androgen-mediated growth was not due to changes in translational capacity. Despite these findings in the limb skeletal muscle, rapamycin completely prevented the ND-mediated growth of the heart. In all, these data indicate that mTORC1 has a limited role in the androgen-mediated growth of the limb skeletal muscle; however, mTORC1 was necessary for androgen-mediated growth of heart muscle.

scholarly journals Testosterone Promotes the Proliferation of Chicken Embryonic Myoblasts Via Androgen Receptor Mediated PI3K/Akt Signaling Pathway

2020 ◽  
Vol 21 (3) ◽  
pp. 1152 ◽  
Author(s):  
Dongfeng Li ◽  
Qin Wang ◽  
Kai Shi ◽  
Yinglin Lu ◽  
Debing Yu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Androgen Receptor ◽  
Muscle Development ◽  
Fiber Formation ◽  
Cross Sectional ◽  
Protein Levels ◽  
Proliferative Effect ◽  
Phosphoinositide 3 Kinase

Testosterone (T) is essential for muscle fiber formation and growth. However, the specific mechanism by which T regulates skeletal muscle development in chicken embryos remains unclear. In this study, the role of T in myoblast proliferation both in vivo and in vitro was investigated. Results showed that the T administration significantly increased the ratio of breast muscle and leg muscle. T induced a significant increase in the cross-sectional area (CSA) and density of myofiber and the ratio of PAX7-positive cells in the skeletal muscle. Exogenous T also induced the upregulation of myogenic regulatory factors (MRFs) and cyclin-dependent kinases (CDK2)/Cyclin D1 (CCND1) and protein levels of androgen receptor (AR), p-Akt and PAX7. Furthermore, T treatment significantly promoted myoblasts cultured in vitro entering a new cell cycle and increased PAX7-positive cells. The mRNA and protein expression of AR and PAX7 were upregulated when treated with T compared to that of the control. The addition of T induced proliferation accompanied by increasing AR level as well as PI3K (Phosphoinositide 3-kinase)/Akt activation. However, T-induced proliferation was attenuated by AR, PI3K, and Akt-specific inhibitors. These data indicated that the pro-proliferative effect of T was regulated though AR in response to the activation of PI3K/Akt signalling pathway.

scholarly journals A novel mechanism of myostatin regulation by its alternative splicing variant during myogenesis in avian species

2015 ◽  
Vol 309 (10) ◽  
pp. C650-C659 ◽  
Author(s):  
Sangsu Shin ◽  
Yan Song ◽  
Jinsoo Ahn ◽  
Eunsoo Kim ◽  
Paula Chen ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Muscle Development ◽  
Muscle Growth ◽  
Avian Species ◽  
Negative Regulator ◽  
Cell Proliferation And Differentiation ◽  
Exon 1 ◽  
Splicing Isoforms

Myostatin ( MSTN) is a key negative regulator of muscle growth and development, and an increase of muscle mass is achieved by inhibiting MSTN signaling. In the current study, five alternative splicing isoforms of MSTN mRNAs in avian species were identified in various tissues. Among these five, three truncated forms of myostatin, MSTN-B, -C, and -E created premature stop codons and produced partial MSTN prodomains encoded from exon 1. MSTN-B is the second dominant isoform following full-length MSTN-A, and their expression was dynamically regulated during muscle development of chicken, turkey, and quail in vivo and in vitro. To clarify the function of MSTN-B, two stable cell lines of quail myoblasts (QM7) were generated to overexpress MSTN-A or MSTN-B. Interestingly, MSTN-B promoted both cell proliferation and differentiation similar to the function of the MSTN prodomain to counteract the negative role of MSTN on myogenesis. The coimmunoprecipitation assay revealed that MSTN-B binds to MSTN-A and reduces the generation of mature MSTN. Furthermore, the current study demonstrated that the partial prodomain encoded from exon 1 is critical for binding of MSTN-B to MSTN-A. Altogether, these data imply that alternative splicing isoforms of MSTN could negatively regulate pro-myostatin processing in muscle cells and prevent MSTN-mediated inhibition of myogenesis in avian species.

Eph/Ephrin signalling in skeletal muscle development and regeneration

2014 ◽  
Author(s):  
◽  
Danny A. Stark
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cells ◽  
Tyrosine Kinases ◽  
Muscle Development ◽  
Receptor Tyrosine Kinases ◽  
Repulsive Interaction ◽  
Type I ◽  
Ephrin Ligands

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Skeletal muscle can be isolated into 642 individual muscles and makes up to one third to one half of the mass of the human body. Each of these muscles is specified and patterned prenatally and after birth they will increase in size and take on characteristics suited to each muscle's unique function. To make the muscles functional, each muscle cell must be innervated by a motor neuron, which will also affect the characteristics of the mature muscle. In a healthy adult, muscles will maintain their specialized pattern and function during physiological homeostasis, and will also recapitulate them if the integrity or health of the muscle is disrupted. This repair and regeneration is dependent satellite cells, the skeletal muscle stem cells. In this dissertation, we study a family of receptor tyrosine kinases, Ephs, and their juxtacrine ephrin ligands in the context of skeletal muscle specification and regeneration. First, using a classical ephrin 'stripe' assay to test for contact-mediated repulsion, we found that satellite cells respond to a subset of ephrins with repulsive motility in vitro and that these forward signals through Ephs also promote patterning of differentiating myotubes parallel to ephrin stripes. This pattering can be replicated in a heterologous in vivo system (the hindbrain of the developing quail, where neural crest cells migrate in streams to the branchial arches, and in the forelimb of the developing quail, where presumptive limb myoblasts emigrate from the somite). Second, we present evidence that specific pairwise interactions between Eph receptor tyrosine kinases and ephrin ligands are required to ensure appropriate muscle innervation when it is originally set during postnatal development and when it is recapitulated after muscle or nerve trauma during adulthood. We show expression of a single ephrin, ephrin-A3, exclusively on type I (slow) myofibers shortly after birth, while its receptor EphA8 is only localized to fast motor endplates, suggesting a functional repulsive interaction for motor axon guidance and/or synaptogenesis. Adult EFNA3-/- mutant mice show a significant loss of slow myofibers, while misexpression of ephrin-A3 on fast myofibers results in a switch from a fast fiber type to slow in the context of sciatic nerve injury and regrowth. Third, we show that EphA7 is expressed on satellite cell derived myocytes in vitro, and marks both myocytes and regenerating myofibers in vivo. In the EPHA7 knockout mouse, we find a regeneration defect in a barium chloride injury model starting 3 days post injection in vivo, and that cultured mutant satellite cells are slow to differentiate and divide. Finally, we present other potential Ephs and ephrins that may affect skeletal muscle, such as EphB1 that is expressed on all MyHC-IIb fibers and a subset of MyHC-IIx fibers, and we show a multitude of Ephs and ephrins at the neuromuscular junction that appear to localize on specific myofibers and at different areas of the synapse. We propose that Eph/ephrin signaling, though well studied in development, continues to be important in regulating post natal development, regeneration, and homeostasis of skeletal muscle.

scholarly journals FGF-2–dependent signaling activated in aged human skeletal muscle promotes intramuscular adipogenesis

2021 ◽  
Vol 118 (37) ◽  
pp. e2021013118 ◽  
Author(s):  
Sebastian Mathes ◽  
Alexandra Fahrner ◽  
Umesh Ghoshdastider ◽  
Hannes A. Rüdiger ◽  
Michael Leunig ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcriptional Activation ◽  
Human Skeletal Muscle ◽  
Muscle Growth ◽  
Muscle Cells ◽  
Adeno Associated Virus ◽  
Adult Skeletal Muscle

Aged skeletal muscle is markedly affected by fatty muscle infiltration, and strategies to reduce the occurrence of intramuscular adipocytes are urgently needed. Here, we show that fibroblast growth factor-2 (FGF-2) not only stimulates muscle growth but also promotes intramuscular adipogenesis. Using multiple screening assays upstream and downstream of microRNA (miR)-29a signaling, we located the secreted protein and adipogenic inhibitor SPARC to an FGF-2 signaling pathway that is conserved between skeletal muscle cells from mice and humans and that is activated in skeletal muscle of aged mice and humans. FGF-2 induces the miR-29a/SPARC axis through transcriptional activation of FRA-1, which binds and activates an evolutionary conserved AP-1 site element proximal in the miR-29a promoter. Genetic deletions in muscle cells and adeno-associated virus–mediated overexpression of FGF-2 or SPARC in mouse skeletal muscle revealed that this axis regulates differentiation of fibro/adipogenic progenitors in vitro and intramuscular adipose tissue (IMAT) formation in vivo. Skeletal muscle from human donors aged >75 y versus <55 y showed activation of FGF-2–dependent signaling and increased IMAT. Thus, our data highlights a disparate role of FGF-2 in adult skeletal muscle and reveals a pathway to combat fat accumulation in aged human skeletal muscle.

scholarly journals MiR-34b-5p Mediates the Proliferation and Differentiation of Myoblasts by Targeting IGFBP2

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 360 ◽  
Author(s):  
Wang ◽  
Zhang ◽  
Li ◽  
Abdalla ◽  
Chen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Cycle Progression ◽  
Muscle Development ◽  
Muscle Growth ◽  
Flow Cytometric Analysis ◽  
Luciferase Reporter ◽  
Cycle Progression ◽  
Flow Cytometric ◽  
Proliferation And Differentiation ◽  
Dual Luciferase Reporter Assay

As key post-transcriptional regulators, microRNAs (miRNAs) play an indispensable role in skeletal muscle development. Our previous study suggested that miR-34b-5p and IGFBP2 could have a potential role in skeletal muscle growth. Our goal in this study is to explore the function and regulatory mechanism of miR-34b-5p and IGFBP2 in myogenesis. In this study, the dual-luciferase reporter assay and Western blot analysis showed that IGFBP2 is a direct target of miR-34b-5p. Flow cytometric analysis and EdU assay showed that miR-34b-5p could repress the cell cycle progression of myoblasts, and miR-34b-5p could promote the formation of myotubes by promoting the expression of MyHC. On the contrary, the overexpression of IGFBP2 significantly facilitated the proliferation of myoblasts and hampered the formation of myotubes. Together, our results indicate that miR-34b-5p could mediate the proliferation and differentiation of myoblasts by targeting IGFBP2.

scholarly journals Skeletal muscle development in vertebrate animals

2015 ◽  
Vol 1 (2) ◽  
pp. 139-148
Author(s):  
Md Shahjahan
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Muscle Fibers ◽  
Muscle Growth ◽  
Paraxial Mesoderm ◽  
Meat Production ◽  
Lineage Specification ◽  
Proliferation And Differentiation ◽  
Axial Musculature ◽  
Postnatal Stage

This review covers the pre- and post-natal development of skeletal muscle of vertebrate animals with cellular and molecular levels. The formation of skeletal muscle initiates from paraxial mesoderm during embryogenesis of individuals which develops somites and subsequently forms dermomyotome derived myotome to give rise axial musculature. This process (myogenesis) includes stem and progenitor cell maintenance, lineage specification, and terminal differentiation to form myofibrils consequent muscle fibers which control muscle mass and its multiplication. The main factors of muscle growth are proliferation and differentiation of myogenic cells in prenatal stage and also the growth of satellite cells at postnatal stage. There is no net increase in the number of muscle fibers in vertebrate animals after hatch or birth except fish. The development of muscle is characterized by hyperplasia and hypertrophy in prenatal and postnatal stages of individuals, respectively, through Wnt signalling pathway including environment, nutrition, sex, feed, growth and myogenic regulatory factors. Therefore further studies could elucidate new growth related genes, markers and factors to enhance meat production and enrich knowledge on muscle growth.Asian J. Med. Biol. Res. June 2015, 1(2): 139-148

scholarly journals miR-194-5p negatively regulates the proliferation and differentiation of rabbit skeletal muscle satellite cells

2020 ◽  
Author(s):  
Yu Shi ◽  
Xudong Mao ◽  
Mingcheng Cai ◽  
Shenqiang Hu ◽  
Xiulan Lai ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cells ◽  
Mammalian Species ◽  
Muscle Growth ◽  
Luciferase Reporter ◽  
Stem Cell Population ◽  
Muscle Satellite Cells ◽  
Skeletal Muscle Satellite Cells ◽  
Proliferation And Differentiation

Abstract Skeletal muscle satellite cells (SMSCs), also known as a multipotential stem cell population, play a crucial role during muscle growth and regeneration. In recent years, numerous miRNAs have been associated with the proliferation and differentiation of SMSCs in a number of mammalian species; however, the regulatory mechanisms of miR-194-5p in rabbit SMSCs still remain scarce. In this study, miR-194-5p was first observed to be highly expressed in the rabbit leg muscle. Furthermore, both the mimics and inhibitor of miR-194-5p were used to explore its role in the proliferation and differentiation of rabbit SMSCs cultured in vitro. Results from both EdU and CCK8 assays showed that miR-194-5p inhibited the proliferation of SMSCs. Meanwhile, Mef2c was identified as a target gene of miR-194-5p based on the dual-luciferase reporter assay results. In addition, upregulation of miR-194-5p decreased the expression levels of Mef2c and MyoG during rabbit SMSCs differentiation on Days 3 and 7 of in vitro culture. Taken together, these data demonstrated that miR-194-5p negatively regulates the proliferation and differentiation of rabbit SMSCs by targeting Mef2c.

Sign in / Sign up

Export Citation Format

Share Document