Skeletal Muscle最新文献

{"title":"The SarcoEndoplasmic Reticulum Calcium ATPase (SERCA) pump: a potential target for intervention in aging and skeletal muscle pathologies.","authors":"Hongyang Xu,&nbsp;Holly Van Remmen","doi":"10.1186/s13395-021-00280-7","DOIUrl":"https://doi.org/10.1186/s13395-021-00280-7","url":null,"abstract":"<p><p>As a key regulator of cellular calcium homeostasis, the Sarcoendoplasmic Reticulum Calcium ATPase (SERCA) pump acts to transport calcium ions from the cytosol back to the sarcoplasmic reticulum (SR) following muscle contraction. SERCA function is closely associated with muscle health and function, and SERCA activity is susceptible to muscle pathogenesis. For example, it has been well reported that pathological conditions associated with aging, neurodegeneration, and muscular dystrophy (MD) significantly depress SERCA function with the potential to impair intracellular calcium homeostasis and further contribute to muscle atrophy and weakness. As a result, targeting SERCA activity has attracted attention as a therapeutical method for the treatment of muscle pathologies. The interventions include activation of SERCA activity and genetic overexpression of SERCA. This review will focus on SERCA function and regulation mechanisms and describe how those mechanisms are affected under muscle pathological conditions including elevated oxidative stress induced by aging, muscle disease, or neuromuscular disorders. We also discuss the current progress and therapeutic approaches to targeting SERCA in vivo.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":"11 1","pages":"25"},"PeriodicalIF":4.9,"publicationDate":"2021-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8588740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10516057","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":"Dynamics of myogenic differentiation using a novel Myogenin knock-in reporter mouse","authors":"Maria Benavente-Diaz, Glenda Comai, D. Di Girolamo, Francina Langa, S. Tajbakhsh","doi":"10.1101/2020.12.21.423736","DOIUrl":"https://doi.org/10.1101/2020.12.21.423736","url":null,"abstract":"Background Myogenin is a transcription factor that is expressed during terminal myoblast differentiation in embryonic development and adult muscle regeneration. Investigation of this cell state transition has been hampered by the lack of a sensitive reporter to dynamically track cells during differentiation. Results Here, we report a knock-in mouse line expressing the tdTOMATO fluorescent protein from the endogenous Myogenin locus. Expression of tdTOMATO in Myog ntdTom mice recapitulated endogenous Myogenin expression during embryonic muscle formation and adult regeneration and enabled the isolation of the MYOGENIN + cell population. We also show that tdTOMATO fluorescence allows tracking of differentiating myoblasts in vitro and by intravital imaging in vivo. Lastly, we monitored by live imaging the cell division dynamics of differentiating myoblasts in vitro and showed that a fraction of the MYOGENIN + population can undergo one round of cell division, albeit at a much lower frequency than MYOGENIN − myoblasts. Conclusions We expect that this reporter mouse will be a valuable resource for researchers investigating skeletal muscle biology in developmental and adult contexts.","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":"11 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2020-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48497455","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":"X-linked muscular dystrophy in a Labrador Retriever strain: phenotypic and molecular characterisation.","authors":"Inès Barthélémy,&nbsp;Nadège Calmels,&nbsp;Robert B Weiss,&nbsp;Laurent Tiret,&nbsp;Adeline Vulin,&nbsp;Nicolas Wein,&nbsp;Cécile Peccate,&nbsp;Carole Drougard,&nbsp;Christophe Beroud,&nbsp;Nathalie Deburgrave,&nbsp;Jean-Laurent Thibaud,&nbsp;Catherine Escriou,&nbsp;Isabel Punzón,&nbsp;Luis Garcia,&nbsp;Jean-Claude Kaplan,&nbsp;Kevin M Flanigan,&nbsp;France Leturcq,&nbsp;Stéphane Blot","doi":"10.1186/s13395-020-00239-0","DOIUrl":"https://doi.org/10.1186/s13395-020-00239-0","url":null,"abstract":"<p><strong>Background: </strong>Canine models of Duchenne muscular dystrophy (DMD) are a valuable tool to evaluate potential therapies because they faithfully reproduce the human disease. Several cases of dystrophinopathies have been described in canines, but the Golden Retriever muscular dystrophy (GRMD) model remains the most used in preclinical studies. Here, we report a new spontaneous dystrophinopathy in a Labrador Retriever strain, named Labrador Retriever muscular dystrophy (LRMD).</p><p><strong>Methods: </strong>A colony of LRMD dogs was established from spontaneous cases. Fourteen LRMD dogs were followed-up and compared to the GRMD standard using several functional tests. The disease causing mutation was studied by several molecular techniques and identified using RNA-sequencing.</p><p><strong>Results: </strong>The main clinical features of the GRMD disease were found in LRMD dogs; the functional tests provided data roughly overlapping with those measured in GRMD dogs, with similar inter-individual heterogeneity. The LRMD causal mutation was shown to be a 2.2-Mb inversion disrupting the DMD gene within intron 20 and involving the TMEM47 gene. In skeletal muscle, the Dp71 isoform was ectopically expressed, probably as a consequence of the mutation. We found no evidence of polymorphism in either of the two described modifier genes LTBP4 and Jagged1. No differences were found in Pitpna mRNA expression levels that would explain the inter-individual variability.</p><p><strong>Conclusions: </strong>This study provides a full comparative description of a new spontaneous canine model of dystrophinopathy, found to be phenotypically equivalent to the GRMD model. We report a novel large DNA mutation within the DMD gene and provide evidence that LRMD is a relevant model to pinpoint additional DMD modifier genes.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":"10 1","pages":"23"},"PeriodicalIF":4.9,"publicationDate":"2020-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13395-020-00239-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9710168","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":"Development of a high-throughput screen to identify small molecule enhancers of sarcospan for the treatment of Duchenne muscular dystrophy.","authors":"Cynthia Shu,&nbsp;Ariana N Kaxon-Rupp,&nbsp;Judd R Collado,&nbsp;Robert Damoiseaux,&nbsp;Rachelle H Crosbie","doi":"10.1186/s13395-019-0218-x","DOIUrl":"https://doi.org/10.1186/s13395-019-0218-x","url":null,"abstract":"<p><strong>Background: </strong>Duchenne muscular dystrophy (DMD) is caused by loss of sarcolemma connection to the extracellular matrix. Transgenic overexpression of the transmembrane protein sarcospan (SSPN) in the DMD mdx mouse model significantly reduces disease pathology by restoring membrane adhesion. Identifying SSPN-based therapies has the potential to benefit patients with DMD and other forms of muscular dystrophies caused by deficits in muscle cell adhesion.</p><p><strong>Methods: </strong>Standard cloning methods were used to generate C2C12 myoblasts stably transfected with a fluorescence reporter for human SSPN promoter activity. Assay development and screening were performed in a core facility using liquid handlers and imaging systems specialized for use with a 384-well microplate format. Drug-treated cells were analyzed for target gene expression using quantitative PCR and target protein expression using immunoblotting.</p><p><strong>Results: </strong>We investigated the gene expression profiles of SSPN and its associated proteins during myoblast differentiation into myotubes, revealing an increase in expression after 3 days of differentiation. We created C2C12 muscle cells expressing an EGFP reporter for SSPN promoter activity and observed a comparable increase in reporter levels during differentiation. Assay conditions for high-throughput screening were optimized for a 384-well microplate format and a high-content imager for the visualization of reporter levels. We conducted a screen of 3200 compounds and identified seven hits, which include an overrepresentation of L-type calcium channel antagonists, suggesting that SSPN gene activity is sensitive to calcium. Further validation of a select hit revealed that the calcium channel inhibitor felodipine increased SSPN transcript and protein levels in both wild-type and dystrophin-deficient myotubes, without increasing differentiation.</p><p><strong>Conclusions: </strong>We developed a stable muscle cell line containing the promoter region of the human SSPN protein fused to a fluorescent reporter. Using the reporter cells, we created and validated a scalable, cell-based assay that is able to identify compounds that increase SSPN promoter reporter, transcript, and protein levels in wild-type and dystrophin-deficient muscle cells.</p>","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":"9 1","pages":"32"},"PeriodicalIF":4.9,"publicationDate":"2019-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13395-019-0218-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37451906","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":"mTORC2 affects the maintenance of the muscle stem cell pool","authors":"Nathalie Rion, P. Castets, Shuo Lin, Leonie Enderle, J. Reinhard, M. Rüegg","doi":"10.1186/s13395-019-0217-y","DOIUrl":"https://doi.org/10.1186/s13395-019-0217-y","url":null,"abstract":"","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13395-019-0217-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48773782","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":"miR-1/206 downregulates splicing factor Srsf9 to promote C2C12 differentiation","authors":"Kristen K. Bjorkman, M. Buvoli, Emily K. Pugach, Michael M. Polmear, L. Leinwand","doi":"10.1186/s13395-019-0211-4","DOIUrl":"https://doi.org/10.1186/s13395-019-0211-4","url":null,"abstract":"","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13395-019-0211-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44107730","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":"In memoriam: Susan Abmayr (1956–2019) – “What do we do? Whatever it takes!”","authors":"E. Geisbrecht, M. Baylies","doi":"10.1186/s13395-019-0215-0","DOIUrl":"https://doi.org/10.1186/s13395-019-0215-0","url":null,"abstract":"","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":"135 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2019-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13395-019-0215-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65847453","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":"Two functional variants at 6p21.1 were associated with lean mass","authors":"Yu-Fang Pei, Wen-Zhu Hu, Xiao-Lin Yang, Xin-Tong Wei, Gui-Juan Feng, Hong Zhang, Hui Shen, Q. Tian, H. Deng, Lei Zhang","doi":"10.1186/s13395-019-0212-3","DOIUrl":"https://doi.org/10.1186/s13395-019-0212-3","url":null,"abstract":"","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2019-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13395-019-0212-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42035426","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":"Barium chloride injures myofibers through calcium-induced proteolysis with fragmentation of motor nerves and microvessels","authors":"Aaron B. Morton, C. Norton, N. Jacobsen, Charmain A. Fernando, D. Cornelison, S. Segal","doi":"10.1186/s13395-019-0213-2","DOIUrl":"https://doi.org/10.1186/s13395-019-0213-2","url":null,"abstract":"","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2019-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13395-019-0213-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49456704","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":"LIM and cysteine-rich domains 1 (LMCD1) regulates skeletal muscle hypertrophy, calcium handling, and force","authors":"D. Ferreira, A. Cheng, A. Cheng, Leandro Z. Agudelo, Leandro Z. Agudelo, I. Červenka, T. Chaillou, T. Chaillou, J. Correia, Margareta Porsmyr-Palmertz, M. Izadi, Alicia Hansson, Vicente Martínez-Redondo, Paula Valente-Silva, Amanda T. Pettersson-Klein, J. Estall, M. Robinson, K. Nair, J. Lanner, J. Ruas","doi":"10.1186/s13395-019-0214-1","DOIUrl":"https://doi.org/10.1186/s13395-019-0214-1","url":null,"abstract":"","PeriodicalId":21747,"journal":{"name":"Skeletal Muscle","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2019-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13395-019-0214-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42838714","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}