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Cells Jul 2020Skeletal muscle is an essential tissue that attaches to bones and facilitates body movements. Insulin-like growth factor-1 (IGF-1) is a hormone found in blood that plays... (Review)
Review
Skeletal muscle is an essential tissue that attaches to bones and facilitates body movements. Insulin-like growth factor-1 (IGF-1) is a hormone found in blood that plays an important role in skeletal myogenesis and is importantly associated with muscle mass entity, strength development, and degeneration and increases the proliferative capacity of muscle satellite cells (MSCs). IGF-1R is an IGF-1 receptor with a transmembrane location that activates PI3K/Akt signaling and possesses tyrosine kinase activity, and its expression is significant in terms of myoblast proliferation and normal muscle mass maintenance. IGF-1 synthesis is elevated in MSCs of injured muscles and stimulates MSCs proliferation and myogenic differentiation. Mechanical loading also affects skeletal muscle production by IGF-1, and low IGF-1 levels are associated with low handgrip strength and poor physical performance. IGF-1 is potentially useful in the management of Duchenne muscular dystrophy, muscle atrophy, and promotes neurite development. This review highlights the role of IGF-1 in skeletal muscle, its importance during myogenesis, and its involvement in different disease conditions.
Topics: Cell Differentiation; Humans; Insulin-Like Growth Factor I; Muscle Development; Muscle, Skeletal
PubMed: 32722232
DOI: 10.3390/cells9081773 -
Seminars in Cell & Developmental Biology Aug 2020Animals possess a wide variety of muscle types that support different kinds of movements. Different muscles have distinct locations, morphologies and contractile... (Review)
Review
Animals possess a wide variety of muscle types that support different kinds of movements. Different muscles have distinct locations, morphologies and contractile properties, raising the question of how muscle diversity is generated during development. Normal aging processes and muscle disorders differentially affect particular muscle types, thus understanding how muscles normally develop and are maintained provides insight into alterations in disease and senescence. As muscle structure and basic developmental mechanisms are highly conserved, many important insights into disease mechanisms in humans as well as into basic principles of muscle development have come from model organisms such as Drosophila, zebrafish and mouse. While transcriptional regulation has been characterized to play an important role in myogenesis, there is a growing recognition of the contributions of alternative splicing to myogenesis and the refinement of muscle function. Here we review our current understanding of muscle type specific alternative splicing, using examples of isoforms with distinct functions from both vertebrates and Drosophila. Future exploration of the vast potential of alternative splicing to fine-tune muscle development and function will likely uncover novel mechanisms of isoform-specific regulation and a more holistic understanding of muscle development, disease and aging.
Topics: Alternative Splicing; Animals; Humans; Muscle Development; Muscles; Muscular Diseases
PubMed: 32070639
DOI: 10.1016/j.semcdb.2020.02.003 -
Thyroid : Official Journal of the... May 2022Maternal exercise (ME) improves fetal and offspring muscle development, but mechanisms remain to be established. Since the thyroid hormone (TH) is critical for cell...
Maternal exercise (ME) improves fetal and offspring muscle development, but mechanisms remain to be established. Since the thyroid hormone (TH) is critical for cell differentiation during embryonic development, we hypothesized that ME elevates TH receptor (THR) signaling in embryos, which promotes embryonic myogenesis. Female mice were exercised daily on a treadmill or received a daily TH, triiodothyronine (T3) injection. Embryos (embryonic day 12.5 [E12.5]) and P19 cells were used for studying effects of TH on embryonic myogenesis. TH levels in serum and embryos after ME or T3I were analyzed. Expression of TH signaling related genes and myogenic genes was assessed. THRα binding to the promoters of myogenic genes was investigated by chromatin immunoprecipitation-qantitative polymerase chain reaction (ChIP-qPCR). A CRISPR/CAS9 plasmid was utilized to knock out THRα in P19 cells. ME elevated TH levels in both maternal circulation and embryos, which were correlated with enhanced TH signaling and myogenesis. At E12.5, both myogenic determinants (, ) and myogenic regulatory factors (, ) were upregulated in ME embryos. ME increased THRα content and elevated messenger RNA (mRNA) expression of TH transporter and deiodinase . In addition, the THRα binding to the promoters of / was increased. In P19 embryoid bodies, T3 promoted myogenic differentiation, which was abolished by ablating THRα. Furthermore, maternal daily injection of T3 at a level matching exercised mothers promoted embryonic myogenesis. ME promotes TH delivery to the embryos and enhances embryonic myogenesis, which is partially mediated by enhanced TH signaling in ME embryos.
Topics: Animals; Cell Differentiation; Female; Mice; Monocarboxylic Acid Transporters; Muscle Development; Physical Conditioning, Animal; Pregnancy; Signal Transduction; Symporters; Triiodothyronine
PubMed: 35286177
DOI: 10.1089/thy.2021.0639 -
Molecular & Cellular Proteomics : MCP 2021Many cell surface and secreted proteins are modified by the covalent addition of glycans that play an important role in the development of multicellular organisms. These...
Many cell surface and secreted proteins are modified by the covalent addition of glycans that play an important role in the development of multicellular organisms. These glycan modifications enable communication between cells and the extracellular matrix via interactions with specific glycan-binding lectins and the regulation of receptor-mediated signaling. Aberrant protein glycosylation has been associated with the development of several muscular diseases, suggesting essential glycan- and lectin-mediated functions in myogenesis and muscle development, but our molecular understanding of the precise glycans, catalytic enzymes, and lectins involved remains only partially understood. Here, we quantified dynamic remodeling of the membrane-associated proteome during a time-course of myogenesis in cell culture. We observed wide-spread changes in the abundance of several important lectins and enzymes facilitating glycan biosynthesis. Glycomics-based quantification of released N-linked glycans confirmed remodeling of the glycome consistent with the regulation of glycosyltransferases and glycosidases responsible for their formation including a previously unknown digalactose-to-sialic acid switch supporting a functional role of these glycoepitopes in myogenesis. Furthermore, dynamic quantitative glycoproteomic analysis with multiplexed stable isotope labeling and analysis of enriched glycopeptides with multiple fragmentation approaches identified glycoproteins modified by these regulated glycans including several integrins and growth factor receptors. Myogenesis was also associated with the regulation of several lectins, most notably the upregulation of galectin-1 (LGALS1). CRISPR/Cas9-mediated deletion of Lgals1 inhibited differentiation and myotube formation, suggesting an early functional role of galectin-1 in the myogenic program. Importantly, similar changes in N-glycosylation and the upregulation of galectin-1 during postnatal skeletal muscle development were observed in mice. Treatment of new-born mice with recombinant adeno-associated viruses to overexpress galectin-1 in the musculature resulted in enhanced muscle mass. Our data form a valuable resource to further understand the glycobiology of myogenesis and will aid the development of intervention strategies to promote healthy muscle development or regeneration.
Topics: Animals; Cell Line; Galectin 1; Glycomics; Glycopeptides; Glycosylation; Male; Mice, Inbred C57BL; Muscle Development; Muscle, Skeletal; Protein Processing, Post-Translational; Proteomics; Rats; Mice
PubMed: 33583770
DOI: 10.1074/mcp.RA120.002166 -
Epigenetics Dec 2022Buffalo holds an excellent potential for beef production, and circRNA plays an important role in regulating myogenesis. However, the regulatory mechanism of circRNAs...
Buffalo holds an excellent potential for beef production, and circRNA plays an important role in regulating myogenesis. However, the regulatory mechanism of circRNAs during buffalo skeletal muscle development has not been fully explored. In this study, circRNA expression profiles during the proliferation and differentiation stages of buffalo myoblasts were analysed by RNA-seq. Here, a total of 3,142 circRNAs candidates were identified, and 110 of them were found to be differentially expressed in the proliferation and differentiation stages of buffalo myoblast libraries. We focused on a 347 nt circRNA subsequently named circCLTH. It consists of three exons and is expressed specifically in muscle tissues. It is a highly conserved non-coding RNA with about 95% homology to both the human and the mouse circRNAs. The results of cell experiments and RNA pull-down assays indicated that circCLTH may capture PLEC protein, promote the proliferation and differentiation of myoblasts as well as inhibit apoptosis. Overexpression of circCLTH suggests that circCLTH is involved in the stimulation of skeletal muscle regeneration. In conclusion, we identified a novel noncoding regulator, circCLTH, that promotes proliferation and differentiation of myoblasts and skeletal muscles.
Topics: Cattle; Humans; Mice; Animals; RNA, Circular; Buffaloes; MicroRNAs; DNA Methylation; Muscle Development; Cell Differentiation; Muscle, Skeletal; Regeneration; Cell Proliferation
PubMed: 36043316
DOI: 10.1080/15592294.2022.2117115 -
Cells Nov 2021Rho guanosine triphosphate hydrolases (GTPases) are molecular switches that cycle between an inactive guanosine diphosphate (GDP)-bound and an active guanosine... (Review)
Review
Rho guanosine triphosphate hydrolases (GTPases) are molecular switches that cycle between an inactive guanosine diphosphate (GDP)-bound and an active guanosine triphosphate (GTP)-bound state during signal transduction. As such, they regulate a wide range of both cellular and physiological processes. In this review, we will summarize recent work on the role of Rho GTPase-regulated pathways in skeletal muscle development, regeneration, tissue mass homeostatic balance, and metabolism. In addition, we will present current evidence that links the dysregulation of these GTPases with diseases caused by skeletal muscle dysfunction. Overall, this information underscores the critical role of a number of members of the Rho GTPase subfamily in muscle development and the overall metabolic balance of mammalian species.
Topics: Animals; Homeostasis; Humans; Muscle Development; Muscle, Skeletal; Muscular Diseases; Regeneration; rho GTP-Binding Proteins
PubMed: 34831205
DOI: 10.3390/cells10112984 -
Cells Jun 2020In the fruit fly, , the larval somatic muscles or the adult thoracic flight and leg muscles are the major voluntary locomotory organs. They share several developmental... (Review)
Review
In the fruit fly, , the larval somatic muscles or the adult thoracic flight and leg muscles are the major voluntary locomotory organs. They share several developmental and structural similarities with vertebrate skeletal muscles. To ensure appropriate activity levels for their functions such as hatching in the embryo, crawling in the larva, and jumping and flying in adult flies all muscle components need to be maintained in a functionally stable or homeostatic state despite constant strain. This requires that the muscles develop in a coordinated manner with appropriate connections to other cell types they communicate with. Various signaling pathways as well as extrinsic and intrinsic factors are known to play a role during muscle development, diversification, and homeostasis. In this review, we discuss genetic control mechanisms of muscle contraction, development, and homeostasis with particular emphasis on the contractile unit of the muscle, the sarcomere.
Topics: Animals; Drosophila melanogaster; Homeostasis; Muscle Development
PubMed: 32630420
DOI: 10.3390/cells9061543 -
Cell Communication and Signaling : CCS May 2022Natural antisense RNAs are RNA molecules that are transcribed from the opposite strand of either protein-coding or non-protein coding genes and have the ability to...
BACKGROUND
Natural antisense RNAs are RNA molecules that are transcribed from the opposite strand of either protein-coding or non-protein coding genes and have the ability to regulate the expression of their sense gene or several related genes. However, the roles of natural antisense RNAs in the maintenance and myogenesis of muscle stem cells remain largely unexamined.
METHODS
We analysed myoblast differentiation and regeneration by overexpression and knockdown of Foxk1-AS using lentivirus and adeno-associated virus infection in C2C12 cells and damaged muscle tissues. Muscle injury was induced by BaCl and the regeneration and repair of damaged muscle tissues was assessed by haematoxylin-eosin staining and quantitative real-time PCR. The expression of myogenic differentiation-related genes was verified via quantitative real-time PCR, Western blotting and immunofluorescence staining.
RESULTS
We identified a novel natural antisense RNA, Foxk1-AS, which is transcribed from the opposite strand of Foxk1 DNA and completely incorporated in the 3' UTR of Foxk1. Foxk1-AS targets Foxk1 and functions as a regulator of myogenesis. Overexpression of Foxk1-AS strongly inhibited the expression of Foxk1 in C2C12 cells and in tibialis anterior muscle tissue and promoted myoblast differentiation and the regeneration of muscle fibres damaged by BaCl. Furthermore, overexpression of Foxk1-AS promoted the expression of Mef2c, which is an important transcription factor in the control of muscle gene expression and is negatively regulated by Foxk1.
CONCLUSION
The results indicated that Foxk1-AS represses Foxk1, thereby rescuing Mef2c activity and promoting myogenic differentiation of C2C12 cells and regeneration of damaged muscle fibres. Video Abstract.
Topics: 3' Untranslated Regions; Cell Differentiation; Forkhead Transcription Factors; Muscle Development; RNA, Antisense
PubMed: 35642035
DOI: 10.1186/s12964-022-00896-2 -
International Journal of Molecular... Nov 2021Skeletal muscle development and regeneration rely on the successive activation of specific transcription factors that engage cellular fate, promote commitment, and drive... (Review)
Review
Skeletal muscle development and regeneration rely on the successive activation of specific transcription factors that engage cellular fate, promote commitment, and drive differentiation. Emerging evidence demonstrates that epigenetic regulation of gene expression is crucial for the maintenance of the cell differentiation status upon division and, therefore, to preserve a specific cellular identity. This depends in part on the regulation of chromatin structure and its level of condensation. Chromatin architecture undergoes remodeling through changes in nucleosome composition, such as alterations in histone post-translational modifications or exchange in the type of histone variants. The mechanisms that link histone post-translational modifications and transcriptional regulation have been extensively evaluated in the context of cell fate and differentiation, whereas histone variants have attracted less attention in the field. In this review, we discuss the studies that have provided insights into the role of histone variants in the regulation of myogenic gene expression, myoblast differentiation, and maintenance of muscle cell identity.
Topics: Animals; Cell Differentiation; Chromatin Assembly and Disassembly; Epigenesis, Genetic; Gene Expression Regulation, Developmental; Genetic Variation; Histones; Humans; Muscle Development; MyoD Protein
PubMed: 34884532
DOI: 10.3390/ijms222312727 -
Molecular and Cellular Biology Jan 2022The activity of AMP-activated protein kinase α (AMPKα) is reduced in type 2 diabetes, and type 2 diabetes is associated with muscular atrophy. To date, there is little...
The activity of AMP-activated protein kinase α (AMPKα) is reduced in type 2 diabetes, and type 2 diabetes is associated with muscular atrophy. To date, there is little known about the mechanism by which free fatty acid (FFA) participates in muscular impairment. The purpose of the present study was to explore whether FFA damages myogenesis through the AMPKα-histone deacetylase 4 (HDAC4)-microRNA 206 (miR-206) pathway. The results showed that 1 mM FFA produced lipid accumulation, significantly impaired the insulin signaling pathway, and decreased the myogenic differentiation of C2C12 myoblast cells. FFA reduced the LKB1-AMPKα pathway, and the activation of AMPKα rescued the myogenic impairment caused by FFA (0.05). AMPKα promoted myogenesis by regulating the expression of miR-206 through HDAC4 (0.05) and affected the cell cycle and cell proliferation to promote myogenesis by regulating miR-206 and miR-206's target cyclin D1 gene. In addition, AICAR (5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside) and HDAC4 small interfering RNA (siRNA) promoted myogenic differentiation compared with the FFA group; however, this positive effect was significantly downregulated after transfection with the miR-206 inhibitor. In summary, AMPKα plays positive roles in myogenic differentiation and myogenesis, and FFA decreased myogenic differentiation and myotube formation through the AMPKα-HDAC4-miR-206 pathway.
Topics: AMP-Activated Protein Kinases; Animals; Cell Differentiation; Cell Proliferation; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Mice; MicroRNAs; Muscle Development; Muscle Fibers, Skeletal; Myoblasts; RNA, Small Interfering
PubMed: 34694913
DOI: 10.1128/MCB.00327-21