Skeletal Muscle最新文献

{"title":"Oxidative stress-induced premature senescence and aggravated denervated skeletal muscular atrophy by regulating progerin-p53 interaction.","authors":"Yaoxian Xiang,&nbsp;Zongqi You,&nbsp;Xinying Huang,&nbsp;Junxi Dai,&nbsp;Junpeng Zhang,&nbsp;Shuqi Nie,&nbsp;Lei Xu,&nbsp;Junjian Jiang,&nbsp;Jianguang Xu","doi":"10.1186/s13395-022-00302-y","DOIUrl":"https://doi.org/10.1186/s13395-022-00302-y","url":null,"abstract":"<p><strong>Background: </strong>Progerin elevates atrophic gene expression and helps modify the nuclear membrane to cause severe muscle pathology, which is similar to muscle weakness in the elderly, to alter the development and function of the skeletal muscles. Stress-induced premature senescence (SIPS), a state of cell growth arrest owing to such stimuli as oxidation, can be caused by progerin. However, evidence for whether SIPS-induced progerin accumulation is connected to denervation-induced muscle atrophy is not sufficient.</p><p><strong>Methods: </strong>Flow cytometry and a reactive oxygen species (ROS) as well as inducible nitric oxide synthase (iNOS) inhibitors were used to assess the effect of oxidation on protein (p53), progerin, and nuclear progerin-p53 interaction in the denervated muscles of models of mice suffering from sciatic injury. Loss-of-function approach with the targeted deletion of p53 was used to assess connection among SIPS, denervated muscle atrophy, and fibrogenesis.</p><p><strong>Results: </strong>The augmentation of ROS and iNOS-derived NO in the denervated muscles of models of mice suffering from sciatic injury upregulates p53 and progerin. The abnormal accumulation of progerin in the nuclear membrane as well as the activation of nuclear progerin-p53 interaction triggered premature senescence in the denervated muscle cells of mice. The p53-dependent SIPS in denervated muscles contributes to their atrophy and fibrogenesis.</p><p><strong>Conclusion: </strong>Oxidative stress-triggered premature senescence via nuclear progerin-p53 interaction that promotes denervated skeletal muscular atrophy and fibrogenesis.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":"19"},"PeriodicalIF":4.9,"publicationDate":"2022-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9335985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40559279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulation of Tweak and Fn14 in skeletal muscle of spinal muscular atrophy mice.","authors":"Katharina E Meijboom,&nbsp;Emma R Sutton,&nbsp;Eve McCallion,&nbsp;Emily McFall,&nbsp;Daniel Anthony,&nbsp;Benjamin Edwards,&nbsp;Sabrina Kubinski,&nbsp;Ines Tapken,&nbsp;Ines Bünermann,&nbsp;Gareth Hazell,&nbsp;Nina Ahlskog,&nbsp;Peter Claus,&nbsp;Kay E Davies,&nbsp;Rashmi Kothary,&nbsp;Matthew J A Wood,&nbsp;Melissa Bowerman","doi":"10.1186/s13395-022-00301-z","DOIUrl":"https://doi.org/10.1186/s13395-022-00301-z","url":null,"abstract":"<p><strong>Background: </strong>Spinal muscular atrophy (SMA) is a childhood neuromuscular disorder caused by depletion of the survival motor neuron (SMN) protein. SMA is characterized by the selective death of spinal cord motor neurons, leading to progressive muscle wasting. Loss of skeletal muscle in SMA is a combination of denervation-induced muscle atrophy and intrinsic muscle pathologies. Elucidation of the pathways involved is essential to identify the key molecules that contribute to and sustain muscle pathology. The tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/TNF receptor superfamily member fibroblast growth factor-inducible 14 (Fn14) pathway has been shown to play a critical role in the regulation of denervation-induced muscle atrophy as well as muscle proliferation, differentiation, and metabolism in adults. However, it is not clear whether this pathway would be important in highly dynamic and developing muscle.</p><p><strong>Methods: </strong>We thus investigated the potential role of the TWEAK/Fn14 pathway in SMA muscle pathology, using the severe Taiwanese Smn^-/-; SMN2 and the less severe Smn^2B/- SMA mice, which undergo a progressive neuromuscular decline in the first three post-natal weeks. We also used experimental models of denervation and muscle injury in pre-weaned wild-type (WT) animals and siRNA-mediated knockdown in C2C12 muscle cells to conduct additional mechanistic investigations.</p><p><strong>Results: </strong>Here, we report significantly dysregulated expression of Tweak, Fn14, and previously proposed downstream effectors during disease progression in skeletal muscle of the two SMA mouse models. In addition, siRNA-mediated Smn knockdown in C2C12 myoblasts suggests a genetic interaction between Smn and the TWEAK/Fn14 pathway. Further analyses of SMA, Tweak^-/-, and Fn14^-/- mice revealed dysregulated myopathy, myogenesis, and glucose metabolism pathways as a common skeletal muscle feature, providing further evidence in support of a relationship between the TWEAK/Fn14 pathway and Smn. Finally, administration of the TWEAK/Fn14 agonist Fc-TWEAK improved disease phenotypes in the two SMA mouse models.</p><p><strong>Conclusions: </strong>Our study provides mechanistic insights into potential molecular players that contribute to muscle pathology in SMA and into likely differential responses of the TWEAK/Fn14 pathway in developing muscle.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":"18"},"PeriodicalIF":4.9,"publicationDate":"2022-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40571245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-throughput muscle fiber typing from RNA sequencing data.","authors":"Nikolay Oskolkov,&nbsp;Malgorzata Santel,&nbsp;Hemang M Parikh,&nbsp;Ola Ekström,&nbsp;Gray J Camp,&nbsp;Eri Miyamoto-Mikami,&nbsp;Kristoffer Ström,&nbsp;Bilal Ahmad Mir,&nbsp;Dmytro Kryvokhyzha,&nbsp;Mikko Lehtovirta,&nbsp;Hiroyuki Kobayashi,&nbsp;Ryo Kakigi,&nbsp;Hisashi Naito,&nbsp;Karl-Fredrik Eriksson,&nbsp;Björn Nystedt,&nbsp;Noriyuki Fuku,&nbsp;Barbara Treutlein,&nbsp;Svante Pääbo,&nbsp;Ola Hansson","doi":"10.1186/s13395-022-00299-4","DOIUrl":"https://doi.org/10.1186/s13395-022-00299-4","url":null,"abstract":"<p><strong>Background: </strong>Skeletal muscle fiber type distribution has implications for human health, muscle function, and performance. This knowledge has been gathered using labor-intensive and costly methodology that limited these studies. Here, we present a method based on muscle tissue RNA sequencing data (totRNAseq) to estimate the distribution of skeletal muscle fiber types from frozen human samples, allowing for a larger number of individuals to be tested.</p><p><strong>Methods: </strong>By using single-nuclei RNA sequencing (snRNAseq) data as a reference, cluster expression signatures were produced by averaging gene expression of cluster gene markers and then applying these to totRNAseq data and inferring muscle fiber nuclei type via linear matrix decomposition. This estimate was then compared with fiber type distribution measured by ATPase staining or myosin heavy chain protein isoform distribution of 62 muscle samples in two independent cohorts (n = 39 and 22).</p><p><strong>Results: </strong>The correlation between the sequencing-based method and the other two were r_ATPas = 0.44 [0.13-0.67], [95% CI], and r_myosin = 0.83 [0.61-0.93], with p = 5.70 × 10^-3 and 2.00 × 10^-6, respectively. The deconvolution inference of fiber type composition was accurate even for very low totRNAseq sequencing depths, i.e., down to an average of ~ 10,000 paired-end reads.</p><p><strong>Conclusions: </strong>This new method ( https://github.com/OlaHanssonLab/PredictFiberType ) consequently allows for measurement of fiber type distribution of a larger number of samples using totRNAseq in a cost and labor-efficient way. It is now feasible to study the association between fiber type distribution and e.g. health outcomes in large well-powered studies.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":"16"},"PeriodicalIF":4.9,"publicationDate":"2022-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40577681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Estrogen signaling effects on muscle-specific immune responses through controlling the recruitment and function of macrophages and T cells.","authors":"Zhao Hong Liao,&nbsp;Tao Huang,&nbsp;Jiang Wei Xiao,&nbsp;Rui Cai Gu,&nbsp;Jun Ouyang,&nbsp;Gang Wu,&nbsp;Hua Liao","doi":"10.1186/s13395-022-00298-5","DOIUrl":"https://doi.org/10.1186/s13395-022-00298-5","url":null,"abstract":"","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":"15"},"PeriodicalIF":4.9,"publicationDate":"2022-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40397270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Absence of the Z-disc protein α-actinin-3 impairs the mechanical stability of Actn3KO mouse fast-twitch muscle fibres without altering their contractile properties or twitch kinetics.","authors":"Michael Haug,&nbsp;Barbara Reischl,&nbsp;Stefanie Nübler,&nbsp;Leonit Kiriaev,&nbsp;Davi A G Mázala,&nbsp;Peter J Houweling,&nbsp;Kathryn N North,&nbsp;Oliver Friedrich,&nbsp;Stewart I Head","doi":"10.1186/s13395-022-00295-8","DOIUrl":"https://doi.org/10.1186/s13395-022-00295-8","url":null,"abstract":"<p><strong>Background: </strong>A common polymorphism (R577X) in the ACTN3 gene results in the complete absence of the Z-disc protein α-actinin-3 from fast-twitch muscle fibres in ~ 16% of the world's population. This single gene polymorphism has been subject to strong positive selection pressure during recent human evolution. Previously, using an Actn3KO mouse model, we have shown in fast-twitch muscles, eccentric contractions at L₀ + 20% stretch did not cause eccentric damage. In contrast, L₀ + 30% stretch produced a significant ~ 40% deficit in maximum force; here, we use isolated single fast-twitch skeletal muscle fibres from the Actn3KO mouse to investigate the mechanism underlying this.</p><p><strong>Methods: </strong>Single fast-twitch fibres are separated from the intact muscle by a collagenase digest procedure. We use label-free second harmonic generation (SHG) imaging, ultra-fast video microscopy and skinned fibre measurements from our MyoRobot automated biomechatronics system to study the morphology, visco-elasticity, force production and mechanical strength of single fibres from the Actn3KO mouse. Data are presented as means ± SD and tested for significance using ANOVA.</p><p><strong>Results: </strong>We show that the absence of α-actinin-3 does not affect the visco-elastic properties or myofibrillar force production. Eccentric contractions demonstrated that chemically skinned Actn3KO fibres are mechanically weaker being prone to breakage when eccentrically stretched. Furthermore, SHG images reveal disruptions in the myofibrillar alignment of Actn3KO fast-twitch fibres with an increase in Y-shaped myofibrillar branching.</p><p><strong>Conclusions: </strong>The absence of α-actinin-3 from the Z-disc in fast-twitch fibres disrupts the organisation of the myofibrillar proteins, leading to structural weakness. This provides a mechanistic explanation for our earlier findings that in vitro intact Actn3KO fast-twitch muscles are significantly damaged by L₀ + 30%, but not L₀ + 20%, eccentric contraction strains. Our study also provides a possible mechanistic explanation as to why α-actinin-3-deficient humans have been reported to have a faster decline in muscle function with increasing age, that is, as sarcopenia reduces muscle mass and force output, the eccentric stress on the remaining functional α-actinin-3 deficient fibres will be increased, resulting in fibre breakages.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":"14"},"PeriodicalIF":4.9,"publicationDate":"2022-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40209835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The influence of age, sex, and exercise on autophagy, mitophagy, and lysosome biogenesis in skeletal muscle","authors":"Matthew Triolo, Ashley N. Oliveira, Rita Kumari, D. Hood","doi":"10.1186/s13395-022-00296-7","DOIUrl":"https://doi.org/10.1186/s13395-022-00296-7","url":null,"abstract":"","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":"43 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2022-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65847501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Myotube Analyzer: how to assess myogenic features in muscle stem cells","authors":"Noë, Simon, Corvelyn, Marlies, Willems, Sarah, Costamagna, Domiziana, Aerts, Jean-Marie, Van Campenhout, Anja, Desloovere, Kaat","doi":"10.1186/s13395-022-00297-6","DOIUrl":"https://doi.org/10.1186/s13395-022-00297-6","url":null,"abstract":"The analysis of in vitro cultures of human adult muscle stem cells obtained from biopsies delineates the potential of skeletal muscles and may help to understand altered muscle morphology in patients. In these analyses, the fusion index is a commonly used quantitative metric to assess the myogenic potency of the muscle stem cells. Since the fusion index only partly describes myogenic potency, we developed the Myotube Analyzer tool, which combines the definition of the fusion index with extra features of myonuclei and myotubes obtained from satellite cell cultures. The software contains image adjustment and mask editing functions for preprocessing and semi-automatic segmentation, while other functions can be used to determine the features of nuclei and myotubes. The fusion index and a set of five novel parameters were tested for reliability and validity in a comparison between satellite cell cultures from children with cerebral palsy and typically developing children. These novel parameters quantified extra nucleus and myotube properties and can be used to describe nucleus clustering and myotube shape. Two analyzers who were trained in cell culture defined all parameters using the Myotube Analyzer app. Out of the six parameters, five had good reliability reflected by good intra-class correlation coefficients (> 0.75). Children with cerebral palsy were significantly different from the typically developing children (p < 0.05) for five parameters, and for three of the six parameters, these differences exceeded the minimal detectable differences. The Myotube Analyzer can be used for the analysis of fixed differentiated myoblast cultures with nuclear and MyHC staining. The app can calculate the fusion index, an already existing parameter, but also provides multiple new parameters to comprehensively describe myogenic potential in its output. The raw data used to determine these parameters are also available in the output. The parameters calculated by the tool can be used to detect differences between cultures from children with cerebral palsy and typically developing children. Since the program is open source, users can customize it to fit their own analysis requirements.","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":"162 5","pages":""},"PeriodicalIF":4.9,"publicationDate":"2022-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138507835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alternative splicing diversifies the skeletal muscle transcriptome during prolonged spaceflight","authors":"Mason Henrich, Pin Ha, Yuanyuan Wang, K. Ting, L. Stodieck, C. Soo, John S. Adams, R. Chun","doi":"10.1186/s13395-022-00294-9","DOIUrl":"https://doi.org/10.1186/s13395-022-00294-9","url":null,"abstract":"","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2022-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44565760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth differentiation factor 11 induces skeletal muscle atrophy via a STAT3-dependent mechanism in pulmonary arterial hypertension","authors":"Xiang, Guiling, Ying, Kelu, Jiang, Pan, Jia, Mengping, Sun, Yipeng, Li, Shanqun, Wu, Xiaodan, Hao, Shengyu","doi":"10.1186/s13395-022-00292-x","DOIUrl":"https://doi.org/10.1186/s13395-022-00292-x","url":null,"abstract":"Skeletal muscle wasting is a clinically remarkable phenotypic feature of pulmonary arterial hypertension (PAH) that increases the risk of mortality. Growth differentiation factor 11 (GDF11), centrally involved in PAH pathogenesis, has an inhibitory effect on skeletal muscle growth in other conditions. However, whether GDF11 is involved in the pathogenesis of skeletal muscle wasting in PAH remains unknown. We showed that serum GDF11 levels in patients were increased following PAH. Skeletal muscle wasting in the MCT-treated PAH model is accompanied by an increase in circulating GDF11 levels and local catabolic markers (Fbx32, Trim63, Foxo1, and protease activity). In vitro GDF11 activated phosphorylation of STAT3. Antagonizing STAT3, with Stattic, in vitro and in vivo, could partially reverse proteolytic pathways including STAT3/socs3 and iNOS/NO in GDF11-meditated muscle wasting. Our findings demonstrate that GDF11 contributes to muscle wasting and the inhibition of its downstream molecule STAT3 shows promise as a therapeutic intervention by which muscle atrophy may be directly prevented in PAH.","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":"159 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2022-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138507823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Notch signaling network in muscle stem cells during development, homeostasis, and disease","authors":"Gioftsidi, Stamatia, Relaix, Frederic, Mourikis, Philippos","doi":"10.1186/s13395-022-00293-w","DOIUrl":"https://doi.org/10.1186/s13395-022-00293-w","url":null,"abstract":"Skeletal muscle stem cells have a central role in muscle growth and regeneration. They reside as quiescent cells in resting muscle and in response to damage they transiently amplify and fuse to produce new myofibers or self-renew to replenish the stem cell pool. A signaling pathway that is critical in the regulation of all these processes is Notch. Despite the major differences in the anatomical and cellular niches between the embryonic myotome, the adult sarcolemma/basement-membrane interphase, and the regenerating muscle, Notch signaling has evolved to support the context-specific requirements of the muscle cells. In this review, we discuss the diverse ways by which Notch signaling factors and other modifying partners are operating during the lifetime of muscle stem cells to establish an adaptive dynamic network.","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":"159 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2022-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138507824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}