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1.
Yi Chuan ; 41(12): 1110-1118, 2019 Dec 20.
Artigo em Chinês | MEDLINE | ID: mdl-31857282

RESUMO

Myogenesis is a complex physiological process that is mainly involved in the proliferation of myogenic stem cells to form myoblasts, which then differentiated and fused to form multinucleated myotubes. Many proteins have been found to be involved in myoblast fusion, but none of them are muscle-specific fusion proteins. In recent years, two muscle-specific transmembrane proteins, i.e. Myomaker and Myomerger, have been discovered and identified, which can coordinate and promote the fusion of myoblasts and thus participate in the process of myogenesis. In this review, we summarize the research progress of Myomaker and Myomerger in myogenesis, including their expression patterns and functional domains, as well as their participation in myoblast fusion mechanisms, aiming to provide relevant ideas for in-depth study of the myogenesis process and treatment of diseases related to myoblast fusion.


Assuntos
Proteínas de Membrana , Músculo Esquelético , Mioblastos , Animais , Diferenciação Celular , Fusão Celular , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Desenvolvimento Muscular , Proteínas Musculares , Músculo Esquelético/citologia , Mioblastos/citologia
2.
Yi Chuan ; 41(12): 1119-1128, 2019 Dec 20.
Artigo em Chinês | MEDLINE | ID: mdl-31857283

RESUMO

Porcine skeletal muscle development is a complex biological process, and differentiation of skeletal muscle satellite cells is an important part of skeletal muscle development. In recent years, it has been found that lncRNA plays an important role in the differentiation of skeletal muscle satellite cells. Here we investigate the effect of lncRNA TCONS_00815878 on the differentiation of porcine skeletal muscle satellite cells. We first used qRT-PCR to detect the expression levels of TCONS_00815878 in six tissues (heart, spleen, lung, kidney, back muscles and leg muscles) of Yorkshire piglets within seven days of birth. At the same time, the expression levels of TCONS_00815878 at five different time points from the embryonic stage to the postnatal stage (35 d, 45 d, 55 d of embryos, and 7 d, 200 d of postpartum leg muscles) were examined. The expression of the differentiation marker genes MyoD, MyoG and MyHC was examined by knocking down TCONS_00815878 in porcine skeletal muscle satellite cells using antisense oligonucleotides (ASO). The target gene of TCONS_00815878 was predicted by bioinformatics analysis, and the function and pathway of its target gene were predicted online using DAVID software. The results showed that TCONS_00815878 had the highest expression level in pig myocardium and leg muscles. Within seven days after birth, TCONS_00815878 increased in the muscle tissue of pigs, and reached the peak of expression level on the 7th day. During the process of proliferation and differentiation of porcine skeletal muscle satellite cells, the expression level of TCONS_00815878 increased during the differentiation stage and peaked at 30 h of differentiation. After knocking down TCONS_00815878, the expression levels of MyoD, MyoG and MyHC were decreased, but the expression level of MyoD was significantly decreased (P<0.05). In addition, functional predictions revealed that the target gene of TCONS_00815878 is enriched in multiple biological processes, such as glycolysis and pyruvate metabolism, related to skeletal muscle satellite cell differentiation. This study speculates that lncRNA TCONS_00815878 may promote the differentiation of porcine skeletal muscle satellite cells.


Assuntos
Diferenciação Celular , Regulação da Expressão Gênica no Desenvolvimento , Músculo Esquelético , RNA Longo não Codificante , Células Satélites de Músculo Esquelético , Animais , Diferenciação Celular/genética , Proliferação de Células , Células Cultivadas , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Desenvolvimento Muscular , Músculo Esquelético/citologia , RNA Longo não Codificante/genética , Células Satélites de Músculo Esquelético/citologia , Suínos
3.
Cell Physiol Biochem ; 53(6): 1029-1045, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31865646

RESUMO

BACKGROUND/AIMS: Fibro-adipogenic progenitors (FAPs), a muscle-resident stem cell population, have recently emerged as important actors of muscle regeneration by interacting with myogenic progenitors (MPs) to promote the formation of new muscle fibers. However, FAPs are also considered as main contributors of intramuscular fibrotic and fat depositions, resulting in a poor quality of muscles and a defective regeneration in aging and Duchenne Muscular Dystrophy disease (DMD). Therefore, the understanding of the control of FAP fate is an important aspect of muscle repair and homeostasis, but little is known in humans. We wondered the extent to which human FAP proliferation, adipogenesis and fibrogenesis can be regulated by human myogenic progenitors (MPs) in physiological and pathological contexts. METHODS: FAPs and MPs were isolated from skeletal muscles of healthy young or old donors and DMD patients. FAP/MP contact co-cultures and conditioned-media from undifferentiated MPs or differentiated myotubes were assessed on both proliferation and fibro-adipogenic differentiation of FAPs. RESULTS: We showed that soluble molecules released by MPs activate the phosphoinositide 3-kinase (PI3Kinase)/Akt pathway in FAPs, resulting in the stimulation of FAP proliferation. FAP differentiation was regulated by MP-derived myotubes through the secretion of pro-fibrogenic factors and anti-adipogenic factors. Importantly, the regulation of FAP adipogenic and fibrogenic fates by myotubes was found to be mediated by Smad2 phosphorylation and the gene expression of glioma-associated oncogene homolog 1 (GLI1). Surprisingly, the regulations of proliferation and differentiation were disrupted for FAPs and MPs derived from aged individuals and patients with DMD. CONCLUSION: Our results highlight a novel crosstalk between FAPs and the myogenic lineage in humans that could be crucial in the formation of adipocyte and myofibroblast accumulation in dystrophic and aged skeletal muscle.


Assuntos
Adipogenia , Desenvolvimento Muscular , Distrofia Muscular de Duchenne/fisiopatologia , Mioblastos/patologia , Adolescente , Adulto , Células-Tronco Adultas/patologia , Idoso , Envelhecimento , Células Cultivadas , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Invest Ophthalmol Vis Sci ; 60(14): 4564-4573, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675425

RESUMO

Purpose: The aim was to clarify the topographical anatomy of the common tendinous ring for the four rectus muscles in both adults and fetuses. Methods: We histologically examined the annular ligament for a common origin of the extraocular rectus muscles using 10 specimens from elderly individuals and 31 embryonic and fetal specimens. Results: At 6 to 8 weeks, each rectus carried an independent long tendon, individually originating from the sphenoid. Notably, we found additional origins from the optic or oculomotor nerve sheath. At 12 to 15 weeks, the lateral, inferior, and medial recti muscles were united to provide a C-shaped musculofibrous mass that was separated from the superior rectus originating from the edge of the optic canal opening. Morphologic features at 31 to 38 weeks were almost the same as those at 12 to 15 weeks, but the long and thick common tendon of the three recti reached the sphenoid body in the parasellar area. In adults, a ring-like arrangement of the rectus muscles ended at a site 8.1 to 12.0 mm anterior to the optic canal opening and independent of the superior rectus origin, the lateral, inferior, and medial recti formed a C-shaped muscle mass. The united origins of the three recti changed to a fibrous band extending along the superomedial wall of the orbital fissure. Conclusions: Consequently, none of the specimens we examined exhibited an annular tendon representing a common origin of the four recti, suggesting that the common tendinous ring includes only medial, lateral, and inferior rectus muscles with the superior rectus taking its origin independently.


Assuntos
Desenvolvimento Fetal/fisiologia , Ligamentos/embriologia , Músculos Oculomotores/embriologia , Órbita/embriologia , Tendões/embriologia , Idoso , Idoso de 80 Anos ou mais , Tecido Conjuntivo/embriologia , Feminino , Idade Gestacional , Humanos , Ligamentos/anatomia & histologia , Masculino , Desenvolvimento Muscular , Junção Neuromuscular , Músculos Oculomotores/anatomia & histologia , Órbita/anatomia & histologia , Tendões/anatomia & histologia
5.
Biochim Biophys Acta Gene Regul Mech ; 1862(10): 194442, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31634638

RESUMO

MyoD is a determining transcription factor involved in myogenic cell differentiation. Post translational modifications of MyoD, including phosphorylation and acetylation, can regulate its transcription activity. Inhibition of protein arginine methyltransferase 1 (PRMT1) leads to insufficient muscle differentiation. However, little is known about arginine methylation in regulating MyoD activity. Here, we demonstrated that MyoD interacts with PRMT1 via its bHLH domain. MyoD could be methylated by PRMT1 at R121. Moreover, R111 and R121 of MyoD are responsible for MyoD-mediated myogenin gene transcription in C2C12 cells. PRMT1 promotes MyoD-mediated myogenin expression, for which the enzymatic activity of PRMT1 is needed. The arginine methylation of MyoD by PRMT1 enhances its DNA binding activity and transactivation. Our data help to further clarify the molecular mechanism of PRMT1 in regulating muscle cell differentiation and provide a new therapeutic target for diseases caused by the abnormal differentiation of muscle cells.


Assuntos
Proteína MyoD/genética , Miogenina/genética , Proteína-Arginina N-Metiltransferases/genética , Proteínas Repressoras/genética , Transcrição Genética , Arginina/genética , Diferenciação Celular/genética , Regulação da Expressão Gênica/genética , Humanos , Metilação , Desenvolvimento Muscular/genética , Processamento de Proteína Pós-Traducional/genética
6.
BMC Complement Altern Med ; 19(1): 287, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31660942

RESUMO

BACKGROUND: Sarcopenia, the decline of skeletal muscle tissue attributed to primary aging is a major concern in older adults. Flavonoids might have potential benefits by modulating the regulation of satellite cells, thus preventing muscle loss. Sinensetin (SIN), a citrus methylated flavone with anti-inflammatory and anti-proliferative activity, can enhance lipolysis. The objective of the present study was to investigate whether SIN might have sarcopenia-suppressing effect on satellite cells from thigh and calf muscle tissues of young and old rats. METHODS: Primary muscle cells were obtained from thigh and calf tissues of young and old group rats by dissection. Obtained satellite cells were incubated with indicated concentrations of SIN (50 and 100 µM) treated and untreated condition in differentiation medium. Morphological changes of cells were examined using a phase-contrast microscope. Protein expression levels of myoD and myogenin were analyzed by Western blot. Cells treated with or without SIN under differentiation condition were also immunocytochemically stained for myogenin and 4',6-diamidino-2-phenylindole (DAPI). RESULTS: Morphologically, the differentiation extracted satellite cells was found to be more evident in SIN treated group of aged rat's cells than that in SIN untreated group. Expression levels of myoD and myogenin proteins involved in myogenesis were increased upon treatment with SIN. CONCLUSIONS: Collectively, our results indicate that SIN can alleviate age-related sarcopenia by increasing differentiation rate and protein levels of myoD and myogenin.


Assuntos
Envelhecimento/efeitos dos fármacos , Flavonoides/farmacologia , Células Musculares/efeitos dos fármacos , Sarcopenia/tratamento farmacológico , Envelhecimento/genética , Envelhecimento/metabolismo , Animais , Células Cultivadas , Humanos , Masculino , Células Musculares/metabolismo , Desenvolvimento Muscular/efeitos dos fármacos , Músculo Esquelético/citologia , Músculo Esquelético/metabolismo , Proteína MyoD/genética , Proteína MyoD/metabolismo , Miogenina/genética , Miogenina/metabolismo , Ratos , Ratos Sprague-Dawley
7.
PLoS Genet ; 15(10): e1008401, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31626630

RESUMO

Wnt signaling regulates primary body axis formation across the Metazoa, with high Wnt signaling specifying posterior identity. Whether a common Wnt-driven transcriptional program accomplishes this broad role is poorly understood. We identified genes acutely affected after Wnt signaling inhibition in the posterior of two regenerative species, the planarian Schmidtea mediterranea and the acoel Hofstenia miamia, which are separated by >550 million years of evolution. Wnt signaling was found to maintain positional information in muscle and regional gene expression in multiple differentiated cell types. sp5, Hox genes, and Wnt pathway components are down-regulated rapidly after ß-catenin RNAi in both species. Brachyury, a vertebrate Wnt target, also displays Wnt-dependent expression in Hofstenia. sp5 inhibits trunk gene expression in the tail of planarians and acoels, promoting separate tail-trunk body domains. A planarian posterior Hox gene, Post-2d, promotes normal tail regeneration. We propose that common regulation of a small gene set-Hox, sp5, and Brachyury-might underlie the widespread utilization of Wnt signaling in primary axis patterning across the Bilateria.


Assuntos
Padronização Corporal/genética , Genes Homeobox/genética , Planárias/genética , Regeneração/genética , Animais , Diferenciação Celular/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Desenvolvimento Muscular/genética , Proteínas Nucleares/genética , Planárias/crescimento & desenvolvimento , Proteínas Wnt/genética , Via de Sinalização Wnt/genética
8.
Adv Exp Med Biol ; 1169: 179-193, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31487024

RESUMO

Tissue-specific stem cells contribute to adult tissue maintenance, repair, and regeneration. In skeletal muscle, many different mononuclear cell types are capable of giving rise to differentiated muscle. Of these tissue stem-like cells, satellite cells (SCs) are the most studied muscle stem cell population and are widely considered the main cellular source driving muscle repair and regeneration in adult tissue. Within the satellite cell pool, many distinct subpopulations exist, each exhibiting differential abilities to exit quiescence, expand, differentiate, and self-renew. In this chapter, we discuss the different stem cell types that can give rise to skeletal muscle tissue and then focus on satellite cell heterogeneity during the process of myogenesis/muscle regeneration. Finally, we highlight emerging opportunities to better characterize muscle stem cell heterogeneity, which will ultimately deepen our appreciation of stem cells in muscle development, repair/regeneration, aging, and disease.


Assuntos
Músculo Esquelético , Células-Tronco , Adulto , Diferenciação Celular , Humanos , Desenvolvimento Muscular , Músculo Esquelético/citologia , Células-Tronco/citologia
9.
Int J Mol Sci ; 20(18)2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31487817

RESUMO

Cyclooxygenases (COXs), including COX-1 and -2, are enzymes essential for lipid mediator (LMs) syntheses from arachidonic acid (AA), such as prostaglandins (PGs). Furthermore, COXs could interplay with other enzymes such as lipoxygenases (LOXs) and cytochrome P450s (CYPs) to regulate the signaling of LMs. In this study, to comprehensively analyze the function of COX-1 and -2 in regulating the signaling of bioactive LMs in skeletal muscle, mouse primary myoblasts and C2C12 cells were transfected with specific COX-1 and -2 siRNAs, followed by targeted lipidomic analysis and customized quantitative PCR gene array analysis. Knocking down COXs, particularly COX-1, significantly reduced the release of PGs from muscle cells, especially PGE2 and PGF2α, as well as oleoylethanolamide (OEA) and arachidonoylethanolamine (AEA). Moreover, COXs could interplay with LOXs to regulate the signaling of hydroxyeicosatetraenoic acids (HETEs). The changes in LMs are associated with the expression of genes, such as Itrp1 (calcium signaling) and Myh7 (myogenic differentiation), in skeletal muscle. In conclusion, both COX-1 and -2 contribute to LMs production during myogenesis in vitro, and COXs could interact with LOXs during this process. These interactions and the fine-tuning of the levels of these LMs are most likely important for skeletal muscle myogenesis, and potentially, muscle repair and regeneration.


Assuntos
Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Desenvolvimento Muscular , Mioblastos Esqueléticos/metabolismo , Transdução de Sinais , Animais , Linhagem Celular , Células Cultivadas , Ciclo-Oxigenase 1/genética , Ciclo-Oxigenase 2/genética , Receptores de Inositol 1,4,5-Trifosfato/genética , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Lipoxigenase/genética , Lipoxigenase/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Mioblastos Esqueléticos/citologia , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo
10.
Int J Mol Sci ; 20(17)2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31484440

RESUMO

The circadian clock has a critical role in many physiological functions of skeletal muscle and is essential to fully understand the precise underlying mechanisms involved in these complex interactions. The importance of circadian expression for structure, function and metabolism of skeletal muscle is clear when observing the muscle phenotype in models of molecular clock disruption. Presently, the maintenance of circadian rhythms is emerging as an important new factor in human health, with disruptions linked to ageing, as well as to the development of many chronic diseases, including sarcopenia. Therefore, the aim of this review is to present the latest findings demonstrating how circadian rhythms in skeletal muscle are important for maintenance of the cellular physiology, metabolism and function of skeletal muscle. Moreover, we will present the current knowledge about the tissue-specific functions of the molecular clock in skeletal muscle.


Assuntos
Desenvolvimento Muscular/fisiologia , Músculo Esquelético/metabolismo , Sarcopenia/metabolismo , Sarcopenia/prevenção & controle , Envelhecimento/fisiologia , Animais , Ritmo Circadiano/fisiologia , Humanos , Desenvolvimento Muscular/genética
11.
J Anim Sci ; 97(10): 4114-4123, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31424542

RESUMO

We hypothesized that oleic acid (OA) in the absence of a thiazolidinedione (i.e., a synthetic peroxisome proliferator-activated receptorγ [PPARγ] agonist) would increase adipogenic gene expression in bovine muscle satellite cells (BSC). The BSC were cultured in differentiation medium containing 10 µM ciglitazone (CI), 100 µM OA, or 100 µM OA plus 10 µM CI (CI-OA). Control (CON) BSC were cultured only in differentiation media (containing 2% horse serum). The presence of myogenin, desmin, and paired box 7 proteins was confirmed in the BSC by immunofluorescence staining, demonstrating that we had isolated myogenic cells. The OA BSC had lesser paired box 3 (Pax3) and myogenic differentiation 1 expression but greater Pax7 and mygogenin (MYOG) expression (P < 0.05), than the CON BSC. The CI BSC had greater Pax3, Pax7, and MYOG expression than CON BSC (P < 0.05), suggesting that CI would promote BSC myogenesis under pro-myogenic conditions (i.e., when cultured with horse serum). However, both the OA and CI treatments upregulated the expression of PPARγ, CCAAT/enhancer-binding protein alpha (C/EBPα) and C/EBPß, sterol regulatory element-binding protein 1, lipoprotein lipase, and glycerol-3-phosphate acyltransferase 3 gene expression, as well as media adiponectin concentration (P < 0.05). The CI, OA, and CI-OA treatments also increased triacylglycerol and lipid droplet accumulation, in spite of upregulation (relative to CON BSC) of adenosine monophosphate-activated protein kinase alpha-1, perilipin 2 (PLIN2), and PLIN3 in BSC and downregulation of G protein-coupled protein receptor 43, acyl-CoA synthetase long chain family member 3, and stearoyl-CoA desaturase (P < 0.05). These results indicate that OA in the absence of a synthetic PPARγ agonist can effectively increase adipogenic gene expression in BSC.


Assuntos
Ácido Oleico/administração & dosagem , PPAR gama/metabolismo , Células Satélites de Músculo Esquelético/metabolismo , Adipogenia/genética , Adiponectina/análise , Animais , Bovinos , Diferenciação Celular , Células Cultivadas , Meios de Cultura , Regulação para Baixo , Imunofluorescência , Expressão Gênica , Metabolismo dos Lipídeos/genética , Desenvolvimento Muscular/genética , Miogenina/genética , Miogenina/metabolismo , PPAR gama/agonistas , PPAR gama/genética , RNA/análise , RNA/isolamento & purificação , Células Satélites de Músculo Esquelético/citologia , Estearoil-CoA Dessaturase/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Tiazolidinedionas/farmacologia , Triglicerídeos/análise , Triglicerídeos/metabolismo
12.
Int J Mol Sci ; 20(16)2019 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-31416143

RESUMO

A series of complex processes regulate muscle development, and lncRNAs play essential roles in the regulation of skeletal myogenesis. Using RNA sequencing, we profiled the lncRNA expression during goat (Capra hircus) skeletal muscle development, which included seven stages across fetal 45 (F45), 65 (F65), 90 (F90), 120 (F120), 135 (F135) days, born for 24 h (B1) and 90 (B90) days. A total of 15,079 lncRNAs were identified in the seven stages, and they were less conservative with other species (human, cow, and mouse). Among them, 547 were differentially expressed, and they divided the seven stages into three functional transition periods. Following weighted gene co-expression network analysis (WGCNA), five lncRNA modules specific for developmental stages were defined as three types: 'Early modules', 'late modules', and 'individual-stage-specific modules'. The enrichment content showed that 'early modules' were related to muscle structure formation, 'late modules' participated in the 'p53 signaling pathway' and other pathways, the F90-highly related module was involved in the 'MAPK signaling pathway', and other pathways. Furthermore, we identified hub-lncRNA in three types of modules, and LNC_011371, LNC_ 007561, and LNC_001728 may play important roles in goat skeletal muscle. These data will facilitate further exploration of skeletal muscle lncRNA functions at different developmental stages in goats.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Cabras/genética , Desenvolvimento Muscular/genética , Músculo Esquelético/metabolismo , RNA Longo não Codificante/genética , Animais , Biomarcadores , Diferenciação Celular/genética , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Sequenciamento de Nucleotídeos em Larga Escala , RNA Mensageiro/genética , Reprodutibilidade dos Testes , Transdução de Sinais , Transcriptoma
13.
Int J Mol Sci ; 20(16)2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31412558

RESUMO

Pluripotent stem cells convert into skeletal muscle tissue during teratoma formation or chimeric animal development. Thus, they are characterized by naive myogenic potential. Numerous attempts have been made to develop protocols enabling efficient and safe conversion of pluripotent stem cells into functional myogenic cells in vitro. Despite significant progress in the field, generation of myogenic cells from pluripotent stem cells is still challenging-i.e., currently available methods require genetic modifications, animal-derived reagents, or are long lasting-and, therefore, should be further improved. In the current study, we investigated the influence of interleukin 4, a factor regulating inter alia migration and fusion of myogenic cells and necessary for proper skeletal muscle development and maintenance, on pluripotent stem cells. We assessed the impact of interleukin 4 on proliferation, selected gene expression, and ability to fuse in case of both undifferentiated and differentiating mouse embryonic stem cells. Our results revealed that interleukin 4 slightly improves fusion of pluripotent stem cells with myoblasts leading to the formation of hybrid myotubes. Moreover, it increases the level of early myogenic genes such as Mesogenin1, Pax3, and Pax7 in differentiating embryonic stem cells. Thus, interleukin 4 moderately enhances competence of mouse pluripotent stem cells for myogenic conversion.


Assuntos
Interleucina-4/metabolismo , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/metabolismo , Animais , Diferenciação Celular/genética , Linhagem Celular , Autorrenovação Celular/genética , Técnicas de Cocultura , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/efeitos dos fármacos , Células-Tronco Embrionárias/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Interleucina-4/genética , Interleucina-4/farmacologia , Camundongos , Desenvolvimento Muscular , Fibras Musculares Esqueléticas/citologia , Fibras Musculares Esqueléticas/metabolismo , Mioblastos/citologia , Mioblastos/efeitos dos fármacos , Mioblastos/metabolismo , Células-Tronco Pluripotentes/efeitos dos fármacos
14.
Biochim Biophys Acta Gene Regul Mech ; 1862(8): 807-821, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31323434

RESUMO

Many protein coding and non-coding genes interplay in governing skeletal muscle formation. Nevertheless, comparing with the linear transcripts, functions of covalently closed circular RNAs (circRNAs), the new frontier of regulatory non-coding RNA (ncRNAs) molecules, remain largely unknown. Here, we identify CDR1as (antisense to the cerebellar degeneration-related protein 1 transcript, also termed as ciRS-7), a well-known cancer and neuron circRNA, plays a significant role in virtually controlling muscle differentiation. CDR1as is highly expressed in muscles of the mid-embryonic goat foetus, and activated at the initiation of myogenic differentiation in vitro. MyoD (myogenic differentiation protein 1), a driven transcription factor for myogenesis, promotes CDR1as by binding on its 5' flank region (-646 to -634 bp, neighbouring the predicted transcription start site at -580 bp). Overexpression or knockdown of CDR1as dramatically induces or impedes muscle differentiation program, respectively. By competitively binding to miR-7 (microRNA 7), CDR1as relieves the downregulation of IGF1R (insulin like growth factor 1 receptor) caused by miR-7 and consequently activates muscle differentiation. These results unveil that CDR1as plays critical roles in myogenic differentiation, which extends the versatile functions of CDR1as in mammal development and disease.


Assuntos
Desenvolvimento Muscular , Proteína MyoD/metabolismo , RNA/genética , Células Satélites de Músculo Esquelético/citologia , Animais , Células Cultivadas , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Cabras , Fator de Crescimento Insulin-Like I/metabolismo , Células Satélites de Músculo Esquelético/metabolismo , Ovinos , Regulação para Cima
15.
Int J Mol Sci ; 20(13)2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31277245

RESUMO

Delta like non-canonical Notch ligand 1 (Dlk1) is a paternally expressed gene which is also known as preadipocyte factor 1 (Pref-1). The accumulation of adipocytes and expression of Dlk1 in regenerating muscle suggests a correlation between fat accumulation and Dlk1 expression in the muscle. Additionally, mice overexpressing Dlk1 show increased muscle weight, while Dlk1-null mice exhibit decreased body weight and muscle mass, indicating that Dlk1 is a critical factor in regulating skeletal muscle mass during development. The muscle regeneration process shares some features with muscle development. However, the role of Dlk1 in regeneration processes remains controversial. Here, we show that mesenchymal progenitors also known as adipocyte progenitors exclusively express Dlk1 during muscle regeneration. Eliminating developmental effects, we used conditional depletion models to examine the specific roles of Dlk1 in muscle stem cells or mesenchymal progenitors. Unexpectedly, deletion of Dlk1 in neither the muscle stem cells nor the mesenchymal progenitors affected the regenerative ability of skeletal muscle. In addition, fat accumulation was not increased by the loss of Dlk1. Collectively, Dlk1 plays essential roles in muscle development, but does not greatly impact regeneration processes and adipogenic differentiation in adult skeletal muscle regeneration.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Músculo Esquelético/fisiologia , Regeneração , Células-Tronco/metabolismo , Animais , Proteínas de Ligação ao Cálcio/fisiologia , Camundongos , Camundongos Knockout , Desenvolvimento Muscular , Células-Tronco/fisiologia
16.
Cells ; 8(7)2019 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-31261950

RESUMO

Accumulating studies report that microRNAs (miRNAs) are actively involved in skeletal myogenesis. Previously, our study revealed that miR-146b-3p was related to the growth of skeletal muscle. Here, we further report that miR-146b-3p is essential for the proliferation, differentiation, and apoptosis of chicken myoblast. Elevated expression of miR-146b-3p can dramatically suppress proliferation and differentiation, and facilitate apoptosis of chicken myoblast. Besides, we identified two target genes of miR-146b-3p, AKT1 and MDFIC, and found that miR-146b-3p can inhibit the PI3K/AKT pathway. Our study also showed that both AKT1 and MDFIC can promote the proliferation and differentiation while inhibit the apoptosis of myoblast in chicken. Overall, our results demonstrate that miR-146b-3p, directly suppressing PI3K/AKT pathway and MDFIC, acts in the proliferation, differentiation, and apoptosis of myoblast in chicken.


Assuntos
MicroRNAs/metabolismo , Desenvolvimento Muscular/genética , Mioblastos/fisiologia , Fatores de Regulação Miogênica/genética , Proteínas Proto-Oncogênicas c-akt/genética , Animais , Apoptose/genética , Diferenciação Celular/genética , Proliferação de Células/genética , Embrião de Galinha , Regulação da Expressão Gênica no Desenvolvimento , Músculo Esquelético/citologia , Músculo Esquelético/embriologia , Fatores de Regulação Miogênica/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/genética
17.
Mol Biol (Mosk) ; 53(3): 436-445, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31184609

RESUMO

N^(6)-methyladenosine (m^(6)A) has been identified as a conserved epitranscriptomic modification of eukaryotic mRNAs, and plays important biological roles in the regulation of cellular metabolic processes. However, its role in myogenic differentiation is unclear. Here, we altered the m^(6)A RNA methylation level by overexpression of METTL3, and explored the effect of m^(6)A RNA methylation on myogenic differentiation of murine myoblasts in vitro. The m6A RNA methylation level is regulated by exogenous methylation inhibitor cycloleucine (Cyc) and methyl donor betaine (Bet). Therefore, chemical reagents of Cyc and Bet were used to test the regulatory effect of m^(6)A RNA methylation on myogenic differentiation. Results showed that METTL3 and Bet positively regulated the m^(6)A RNA methylation levels, and Cyc negatively regulated m^(6)A RNA methylation levels. In addition, m^(6)A methylation positively regulated myogenic differentiation in murine myoblasts. These findings provide insight in the mechanisms underlying the effect of m^(6)A RNA methylation on myogenesis.


Assuntos
Diferenciação Celular , Metilação , Metiltransferases/metabolismo , Desenvolvimento Muscular , Mioblastos/citologia , Mioblastos/metabolismo , Animais , Camundongos
18.
Folia Biol (Praha) ; 65(1): 43-52, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31171081

RESUMO

Rhabdomyosarcoma (RMS) is a malignant tumour of soft tissues, occurring mainly in children and young adults. RMS cells derive from muscle cells, which due to mutations and epigenetic modifications have lost their ability to differentiate. Epigenetic modifications regulate expression of genes responsible for cell proliferation, maturation, differentiation and apoptosis. HDAC inhibitors suppress histone acetylation; therefore, they are a promising tool used in cancer therapy. Trichostatin A (TsA) is a pan-inhibitor of HDAC. In our study, we investigated the effect of TsA on RMS cell biology. Our findings strongly suggest that TsA inhibits RMS cell proliferation, induces cell apoptosis, and reactivates tumour cell differentiation. TsA up-regulates miR-27b expression, which is involved in the process of myogenesis. Moreover, TsA increases susceptibility of RMS cells to routinely used chemotherapeutics. In conclusion, TsA exhibits anti-cancer properties, triggers differentiation, and thereby can complement an existing spectrum of chemotherapeutics used in RMS therapy.


Assuntos
Ácidos Hidroxâmicos/farmacologia , Rabdomiossarcoma/metabolismo , Acetilação/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Epigênese Genética/genética , Inibidores de Histona Desacetilases/farmacologia , Humanos , MicroRNAs/metabolismo , Desenvolvimento Muscular/efeitos dos fármacos , Desenvolvimento Muscular/genética
19.
Adv Exp Med Biol ; 1147: 319-344, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31147885

RESUMO

The muscular dystrophies are an heterogeneous group of inherited myopathies characterised by the progressive wasting of skeletal muscle tissue. Pericytes have been shown to make muscle in vitro and to contribute to skeletal muscle regeneration in several animal models, although recent data has shown this to be controversial. In fact, some pericyte subpopulations have been shown to contribute to fibrosis and adipose deposition in muscle. In this chapter, we explore the identity and the multifaceted role of pericytes in dystrophic muscle, potential therapeutic applications and the current need to overcome the hurdles of characterisation (both to identify pericyte subpopulations and track cell fate), to prevent deleterious differentiation towards myogenic-inhibiting subpopulations, and to improve cell proliferation and engraftment efficacy.


Assuntos
Distrofias Musculares , Pericitos , Animais , Diferenciação Celular , Desenvolvimento Muscular , Músculo Esquelético , Regeneração
20.
J Insect Physiol ; 117: 103906, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31254521

RESUMO

There is growing concern about the impact of poor nutrition on honey bee health. With caged bee experiments and whole-colony field experiments, we examined the effects of supplementing bees with essential amino acids (EAA), or a control treatment of nonessential amino acids (NAA). Caged bees fed EAA developed significantly greater head weights than controls, weights that were similar to nurse bees. Caged bees fed EAA developed significantly greater thorax weights than controls, weights that were similar to foragers. Higher head and thorax weights may respectively reflect increased glandular development in nurse bees and higher flight muscle mass in forager bees. In our field study, 29% of the pollen collected by our honey bee colonies came from eucalyptus trees. Amino acid analyses revealed no EAA deficiencies for the bee-collected polyfloral pollen or for monofloral eucalyptus pollen. Colonies fed 29 g EAA supplement may have slightly increased individual bee growth and brood rearing, but this effect was not significant. A clear colony result was a correlation between nurse bee physiology and brood development: 17% increase in nurse bee weight corresponded to 100% more capped brood cells (R2 = 0.38). We suggest that colony supplementation should target nurse bee nutrition. Nurse bees eventually become forager bees. Hence, increased glandular development may support colony brood development and greater flight muscle mass may assist colony foraging.


Assuntos
Aminoácidos , Abelhas/crescimento & desenvolvimento , Desenvolvimento Muscular , Criação de Animais Domésticos , Animais , Suplementos Nutricionais
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