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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 -
Biochemical and Biophysical Research... Nov 2023Skeletal muscle myogenesis represents one of the most intensively and extensively examined systems of cell differentiation, tissue formation, and regeneration. Muscle... (Review)
Review
Skeletal muscle myogenesis represents one of the most intensively and extensively examined systems of cell differentiation, tissue formation, and regeneration. Muscle regeneration provides an in vivo model system of postnatal myogenesis. It comprises multiple steps including muscle stem cell (or satellite cell) quiescence, activation, migration, myogenic determination, myoblast proliferation, myocyte differentiation, myofiber maturation, and hypertrophy. A variety of extracellular signaling and subsequent intracellular signal transduction pathways or networks govern the individual steps of postnatal myogenesis. Among them, MAPK pathways (the ERK, JNK, p38 MAPK, and ERK5 pathways) and PI3K-Akt signaling regulate multiple steps of myogenesis. Ca, cytokine, and Wnt signaling also participate in several myogenesis steps. These signaling pathways often control cell cycle regulatory proteins or the muscle-specific MyoD family and the MEF2 family of transcription factors. This article comprehensively reviews molecular mechanisms of the individual steps of postnatal skeletal muscle myogenesis by focusing on signal transduction pathways or networks. Nevertheless, no or only a partial signaling molecules or pathways have been identified in some responses during myogenesis. The elucidation of these unidentified signaling molecules and pathways leads to an extensive understanding of the molecular mechanisms of myogenesis.
Topics: Cell Differentiation; Mitogen-Activated Protein Kinases; Muscle Development; Muscle Fibers, Skeletal; Muscle, Skeletal; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction
PubMed: 37826946
DOI: 10.1016/j.bbrc.2023.09.048 -
Journal of Cachexia, Sarcopenia and... Apr 2022Most patients with pancreatic cancer develop cachexia, which is characterized by progressive muscle loss. The mechanisms underlying muscle loss in cancer cachexia remain...
BACKGROUND
Most patients with pancreatic cancer develop cachexia, which is characterized by progressive muscle loss. The mechanisms underlying muscle loss in cancer cachexia remain elusive. Pancreatic tumour organoids are 3D cell culture models that retain key characteristics of the parent tumour. We aimed to investigate the effect of pancreatic tumour organoid-derived factors on processes that determine skeletal muscle mass, including the regulation of muscle protein turnover and myogenesis.
METHODS
Conditioned medium (CM) was collected from human pancreatic cancer cell lines (PK-45H, PANC-1, PK-1, and KLM-1), pancreatic tumour organoid cultures from a severely cachectic (PANCO-9a) and a non-cachectic patient (PANCO-12a), and a normal pancreas organoid culture. Differentiating C2C12 myoblasts and mature C2C12 myotubes were exposed to CM for 24 h or maintained in control medium. In myotubes, NF-kB activation was monitored using a NF-κB luciferase reporter construct, and mRNA expression of E3-ubiquitin ligases and REDD1 was analysed by RT-qPCR. C2C12 myoblast proliferation and differentiation were monitored by live cell imaging and myogenic markers and myosin heavy chain (MyHC) isoforms were assessed by RT-qPCR.
RESULTS
Whereas CM from PK-1 and KLM-1 cells significantly induced NF-κB activation in C2C12 myotubes (PK-1: 3.1-fold, P < 0.001; KLM-1: 2.1-fold, P = 0.01), Atrogin-1/MAFbx and MuRF1 mRNA were only minimally and inconsistently upregulated by the CM of pancreatic cancer cell lines. Similarly, E3-ubiquitin ligases and REDD1 mRNA expression in myotubes were not altered by exposure to pancreatic tumour organoid CM. Compared with the control condition, CM from both PANCO-9a and PANCO-12a tumour organoids increased proliferation of myoblasts, which was accompanied by significant downregulation of the satellite cell marker paired-box 7 (PAX7) (PANCO-9a: -2.1-fold, P < 0.001; PANCO-12a: -2.0-fold, P < 0.001) and myogenic factor 5 (MYF5) (PANCO-9a: -2.1-fold, P < 0.001; PANCO-12a: -1.8-fold, P < 0.001) after 48 h of differentiation. Live cell imaging revealed accelerated alignment and fusion of myoblasts exposed to CM from PANCO-9a and PANCO-12a, which was in line with significantly increased Myomaker mRNA expression levels (PANCO-9a: 2.4-fold, P = 0.001; PANCO-12a: 2.2-fold, P = 0.004). These morphological and transcriptional alterations were accompanied by increased expression of muscle differentiation markers such as MyHC-IIB (PANCO-9a: 2.5-fold, P = 0.04; PANCO-12a: 3.1-fold, P = 0.006). Although the impact of organoid CM on myogenesis was not associated with the cachexia phenotype of the donor patients, it was specific for tumour organoids, as CM of control pancreas organoids did not modulate myogenic fusion.
CONCLUSIONS
These data show that pancreatic tumour organoid-derived factors alter the kinetics of myogenesis, which may eventually contribute to impaired muscle mass maintenance in cancer cachexia.
Topics: Cachexia; Humans; Muscle Development; Myoblasts; Organoids; Pancreatic Neoplasms
PubMed: 35146962
DOI: 10.1002/jcsm.12917 -
Journal of Molecular Histology Aug 2021Tongue muscles are derived from mesodermal cells, while signals driven by cranial neural crest cells (CNCCs) regulate tongue myogenesis via tissue-tissue interaction....
Tongue muscles are derived from mesodermal cells, while signals driven by cranial neural crest cells (CNCCs) regulate tongue myogenesis via tissue-tissue interaction. Based on such mechanisms of interaction, congenital tongue defects occur in CNC-related syndromes in humans. This study utilized a pathologic model for the syndrome of congenital bony syngnathia, Wnt1-Cre;pMes-Bmp4 mouse line, to explore impacts of enhanced CNCCs-originated BMP4 signal on tongue myogenesis via tissue-tissue interaction. Our results revealed that microglossia, a clinical phenotype of congenital bony syngnathia in humans exhibited in Wnt1-Cre;pMes-Bmp4 mice due to impaired myogenesis. The augmented BMP4 signal affected the distal distribution, proliferation, and differentiation of myogenic cells as well as tendon patterning, resulting in disarrangement and atrophy of tongue muscles and the loss of the anterior digastric muscle. This study demonstrated how a CNCCs-originated ligand impaired tongue myogenesis via a non-autonomous way, which provided potential formation mechanisms for understanding tongue abnormalities in CNC-related syndromes.
Topics: Animals; Bone Morphogenetic Protein 4; Cell Differentiation; Cell Movement; Cell Proliferation; Gene Expression Regulation, Developmental; Immunohistochemistry; In Situ Hybridization; Mice; Mice, Transgenic; Muscle Development; Neural Crest; Signal Transduction; Tongue; Tongue Diseases
PubMed: 34076834
DOI: 10.1007/s10735-021-09987-9 -
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 -
Gene Mar 2020Muscles are critical tissues for mammals due to their close association with movement and physiology. Myogenesis involves proliferation, differentiation, and fusion of... (Review)
Review
Muscles are critical tissues for mammals due to their close association with movement and physiology. Myogenesis involves proliferation, differentiation, and fusion of myoblast, in which many well-known protein-coding genes, as well as linear non-coding RNAs such as microRNAs (miRNAs), are involved. Recently, circular RNAs (circRNAs) have attracted much attention since several circRNAs are known to play significant roles in muscle development and diseases through limited mechanisms, particularly through sponging miRNAs. Through advanced researches, increasing evidence suggests that Cerebellar Degeneration-Related protein 1 antisense (CDR1as) is an important circRNA that regulates the levels of mRNAs expression via competitively sponged miRNAs. Here, we reviewed the robust expression and base pairing relationships of CDR1as and several myogenic miRNAs, as well as these miRNAs and their targeted genes in muscles or some muscle-related diseases. These potential CDR1as/miRNAs/mRNA pathways will provide the basis for further research on the function of CDR1as in muscle development, and eventually extend the versatile roles of CDR1as in mammals.
Topics: Animals; Cell Differentiation; Gene Expression Regulation; Humans; MicroRNAs; Muscle Development; Myoblasts; RNA; RNA, Circular; RNA, Long Noncoding; RNA, Messenger
PubMed: 31904497
DOI: 10.1016/j.gene.2019.144315 -
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 -
Frontiers in Neuroendocrinology Oct 2023Androgens' pleiotropic actions in promoting sex differences present not only a challenge to providing a comprehensive account of their function, but also an opportunity... (Review)
Review
Androgens' pleiotropic actions in promoting sex differences present not only a challenge to providing a comprehensive account of their function, but also an opportunity to gain insights by comparing androgenic actions across organ systems. Although often overlooked by neuroscientists, skeletal muscle is another androgen-responsive organ system which shares with the nervous system properties of electrochemical excitability, behavioral relevance, and remarkable capacity for adaptive plasticity. Here we review androgenic regulation of mitogenic plasticity in skeletal muscle with the goal of identifying areas of interest to those researching androgenic mechanisms mediating sexual differentiation of neurogenesis. We use an organizational-activational framework to relate broad areas of similarity and difference between androgen effects on mitogenesis in muscle and brain throughout the lifespan, from early organogenesis, through pubertal organization, adult activation, and aging. The focus of the review is androgenic regulation of muscle-specific stem cells (satellite cells), which share with neural stem cells essential functions in development, plasticity, and repair, albeit with distinct, muscle-specific features. Also considered are areas of paracrine and endocrine interaction between androgen action on muscle and nervous system, including mediation of neural plasticity of innervating and distal neural populations by muscle-produced trophic factors.
Topics: Female; Male; Humans; Androgens; Receptors, Androgen; Longevity; Neurogenesis; Muscle, Skeletal; Muscle Development
PubMed: 37669703
DOI: 10.1016/j.yfrne.2023.101101 -
Scientific Reports Oct 2020Muscle wasting and atrophy are regulated by multiple molecular processes, including mRNA processing. Reduced levels of the polyadenylation binding protein nucleus 1...
Muscle wasting and atrophy are regulated by multiple molecular processes, including mRNA processing. Reduced levels of the polyadenylation binding protein nucleus 1 (PABPN1), a multifactorial regulator of mRNA processing, cause muscle atrophy. A proteomic study in muscles with reduced PABPN1 levels suggested dysregulation of sarcomeric and cytoskeletal proteins. Here we investigated the hypothesis that reduced PABPN1 levels lead to an aberrant organization of the cytoskeleton. MURC, a plasma membrane-associated protein, was found to be more abundant in muscles with reduced PABPN1 levels, and it was found to be expressed at regions showing regeneration. A polarized cytoskeletal organization is typical for muscle cells, but muscle cells with reduced PABPN1 levels (named as shPAB) were characterized by a disorganized cytoskeleton that lacked polarization. Moreover, cell mechanical features and myogenic differentiation were significantly reduced in shPAB cells. Importantly, restoring cytoskeletal stability, by actin overexpression, was beneficial for myogenesis, expression of sarcomeric proteins and proper localization of MURC in shPAB cell cultures and in shPAB muscle bundle. We suggest that poor cytoskeletal mechanical features are caused by altered expression levels of cytoskeletal proteins and contribute to muscle wasting and atrophy.
Topics: Actins; Cell Line; Cytoskeleton; Humans; Muscle Development; Muscle, Skeletal; Muscular Atrophy; Poly(A)-Binding Protein I
PubMed: 33077830
DOI: 10.1038/s41598-020-74676-8