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Skeletal Muscle

Monica Llano-Diez, Wen Fury, Haruka Okamoto, Yu Bai, Jesper Gromada, Lars Larsson
BACKGROUND: Critical illness myopathy (CIM) is associated with severe skeletal muscle wasting and impaired function in intensive care unit (ICU) patients. The mechanisms underlying CIM remain incompletely understood. To elucidate the biological activities occurring at the transcriptional level in the skeletal muscle of ICU patients with CIM, the gene expression profiles, potential upstream regulators, and enrichment pathways were characterized using RNA sequencing (RNA-seq). We also compared the skeletal muscle gene signatures in ICU patients with CIM and genes perturbed by mechanical loading in one leg of the ICU patients, with an aim of reducing the loss of muscle function...
April 16, 2019: Skeletal Muscle
Dong Liu, Xinran Qiao, Zhijuan Ge, Yue Shang, Yi Li, Wendie Wang, Minghua Chen, Shuyi Si, Shu-Zhen Chen
BACKGROUND: Cancer cachexia as a metabolic syndrome can lead to at least 25% of cancer deaths. The inhibition of muscle atrophy is a main strategy to treat cancer cachexia. In this process, myostatin (MSTN) can exert a dual effect on protein metabolism, including inhibition of protein biosynthesis and enhancement of protein degradation. In this study, we will test the effect on muscle atrophy induced by cancer cachexia of IMB0901, a MSTN inhibitor. METHODS: Two high-throughput screening models against MSTN were developed...
March 28, 2019: Skeletal Muscle
Lindsey A Lee, Anastasia Karabina, Lindsey J Broadwell, Leslie A Leinwand
Striated muscles express an array of sarcomeric myosin motors that are tuned to accomplish specific tasks. Each myosin isoform found in muscle fibers confers unique contractile properties to the fiber in order to meet the demands of the muscle. The sarcomeric myosin heavy chain (MYH) genes expressed in the major cardiac and skeletal muscles have been studied for decades. However, three ancient myosins, MYH7b, MYH15, and MYH16, remained uncharacterized due to their unique expression patterns in common mammalian model organisms and due to their relatively recent discovery in these genomes...
March 5, 2019: Skeletal Muscle
Dimuthu K Wasgewatte Wijesinghe, Eleanor J Mackie, Charles N Pagel
BACKGROUND: Osteopontin is secreted by skeletal muscle myoblasts and macrophages, and its expression is upregulated in muscle following injury. Osteopontin is present in many different structural forms, which vary in their expression patterns and effects on cells. Using a whole muscle autograft model of muscle injury in mice, we have previously shown that inflammation and regeneration of muscle following injury are delayed by the absence of osteopontin. The current study was undertaken to determine whether muscle or non-muscle cells provide the source of osteopontin required for its role in muscle regeneration...
February 26, 2019: Skeletal Muscle
Giselle A Joseph, Margaret Hung, Aviva J Goel, Mingi Hong, Marysia-Kolbe Rieder, Noam D Beckmann, Madhavika N Serasinghe, Jerry E Chipuk, Parvathi M Devarakonda, David J Goldhamer, Paulina Aldana-Hernandez, Jonathan Curtis, René L Jacobs, Robert S Krauss
BACKGROUND: Group I Paks are serine/threonine kinases that function as major effectors of the small GTPases Rac1 and Cdc42, and they regulate cytoskeletal dynamics, cell polarity, and transcription. We previously demonstrated that Pak1 and Pak2 function redundantly to promote skeletal myoblast differentiation during postnatal development and regeneration in mice. However, the roles of Pak1 and Pak2 in adult muscle homeostasis are unknown. Choline kinase β (Chk β) is important for adult muscle homeostasis, as autosomal recessive mutations in CHKβ are associated with two human muscle diseases, megaconial congenital muscular dystrophy and proximal myopathy with focal depletion of mitochondria...
February 21, 2019: Skeletal Muscle
Taejeong Song, Palanikumar Manoharan, Douglas P Millay, Sheryl E Koch, Jack Rubinstein, Judith A Heiny, Sakthivel Sadayappan
BACKGROUND: Skeletal muscle myopathy and exercise intolerance are diagnostic hallmarks of heart failure (HF). However, the molecular adaptations of skeletal muscles during dilated cardiomyopathy (DCM)-mediated HF are not completely understood. METHODS: Skeletal muscle structure and function were compared in wild-type (WT) and cardiac myosin binding protein-C null mice (t/t), which develop DCM-induced HF. Cardiac function was examined by echocardiography. Exercise tolerance was measured using a graded maximum treadmill running test...
January 24, 2019: Skeletal Muscle
Pengfei Cui, Wei Shao, Caihua Huang, Chang-Jer Wu, Bin Jiang, Donghai Lin
BACKGROUND: Cachexia is a complex metabolic disorder and muscle atrophy syndrome, impacting 80% patients with advanced cancers. Malignant glioma is considered to be one of the deadliest human cancers, accounting for about 60% of all primary brain tumors. However, cachexia symptoms induced by glioma have received little attention. This work aims to explore skeletal muscle atrophy in orthotopic glioma murine models. METHODS: BALB/c nude mice were orthotopicly implanted with normal glial (HEB) and glioma (WHO II CHG5 and WHO IV U87) cells...
January 11, 2019: Skeletal Muscle
Thibaut Desgeorges, Sophie Liot, Solene Lyon, Jessica Bouvière, Alix Kemmel, Aurélie Trignol, David Rousseau, Bruno Chapuis, Julien Gondin, Rémi Mounier, Bénédicte Chazaud, Gaëtan Juban
Adult skeletal muscle is capable of complete regeneration after an acute injury. The main parameter studied to assess muscle regeneration efficacy is the cross-sectional area (CSA) of the myofibers as myofiber size correlates with muscle force. CSA analysis can be time-consuming and may trigger variability in the results when performed manually. This is why programs were developed to completely automate the analysis of the CSA, such as SMASH, MyoVision, or MuscleJ softwares. Although these softwares are efficient to measure CSA on normal or hypertrophic/atrophic muscle, they fail to efficiently measure CSA on regenerating muscles...
January 8, 2019: Skeletal Muscle
V Michailowsky, H Li, B Mittra, S R Iyer, D A G Mazála, M Corrotte, Y Wang, E R Chin, R M Lovering, N W Andrews
BACKGROUND: Niemann-Pick disease type A (NPDA), a disease caused by mutations in acid sphingomyelinase (ASM), involves severe neurodegeneration and early death. Intracellular lipid accumulation and plasma membrane alterations are implicated in the pathology. ASM is also linked to the mechanism of plasma membrane repair, so we investigated the impact of ASM deficiency in skeletal muscle, a tissue that undergoes frequent cycles of injury and repair in vivo. METHODS: Utilizing the NPDA/B mouse model ASM-/- and wild type (WT) littermates, we performed excitation-contraction coupling/Ca2+ mobilization and sarcolemma injury/repair assays with isolated flexor digitorum brevis fibers, proteomic analyses with quadriceps femoris, flexor digitorum brevis, and tibialis posterior muscle and in vivo tests of the contractile force (maximal isometric torque) of the quadriceps femoris muscle before and after eccentric contraction-induced muscle injury...
January 5, 2019: Skeletal Muscle
Jihee Kim, Chad A Grotegut, James W Wisler, Tianyu Li, Lan Mao, Minyong Chen, Wei Chen, Paul B Rosenberg, Howard A Rockman, Robert J Lefkowitz
BACKGROUND: β2 -adrenergic receptors (β2 ARs) are the target of catecholamines and play fundamental roles in cardiovascular, pulmonary, and skeletal muscle physiology. An important action of β2 AR stimulation on skeletal muscle is anabolic growth, which has led to the use of agonists such as clenbuterol by athletes to enhance muscle performance. While previous work has demonstrated that β2 ARs can engage distinct signaling and functional cascades mediated by either G proteins or the multifunctional adaptor protein, β-arrestin, the precise role of β-arrestin in skeletal muscle physiology is not known...
December 27, 2018: Skeletal Muscle
Andrew N Billin, Samuel E Honeycutt, Alan V McDougal, Jaclyn P Kerr, Zhe Chen, Johannes M Freudenberg, Deepak K Rajpal, Guizhen Luo, Henning Fritz Kramer, Robert S Geske, Frank Fang, Bert Yao, Richard V Clark, John Lepore, Alex Cobitz, Ram Miller, Kazunori Nosaka, Aaron C Hinken, Alan J Russell
Following publication of the original article [1], the authors flagged that there is a discrepancy with the Availability of data and materials statement on page 12 of the article.
December 10, 2018: Skeletal Muscle
Hema Bye-A-Jee, Dhamayanthi Pugazhendhi, Samuel Woodhouse, Patrick Brien, Rachel Watson, Martin Turner, Jennifer Pell
BACKGROUND: Members of the ZFP36 family of RNA-binding proteins regulate gene expression post-transcriptionally by binding to AU-rich elements in the 3'UTR of mRNA and stimulating mRNA degradation. The proteins within this family target different transcripts in different tissues. In particular, ZFP36 targets myogenic transcripts and may have a role in adult muscle stem cell quiescence. Our study examined the requirement of ZFP36L1 and ZFP36L2 in adult muscle cell fate regulation. METHODS: We generated single and double conditional knockout mice in which Zfp36l1 and/or Zfp36l2 were deleted in Pax7-expressing cells...
December 7, 2018: Skeletal Muscle
Aman Patel, Junling Zhao, Yongping Yue, Keqing Zhang, Dongsheng Duan, Yi Lai
BACKGROUND: Loss of sarcolemmal nNOSμ is a common manifestation in a wide variety of muscle diseases and contributes to the dysregulation of multiple muscle activities. Given the critical role sarcolemmal nNOSμ plays in muscle, restoration of sarcolemmal nNOSμ should be considered as an important therapeutic goal. METHODS: nNOSμ is anchored to the sarcolemma by dystrophin spectrin-like repeats 16 and 17 (R16/17) and the syntrophin PDZ domain (Syn PDZ). To develop a strategy that can independently restore sarcolemmal nNOSμ, we engineered an R16/17-Syn PDZ fusion construct and tested whether this construct alone is sufficient to anchor nNOSμ to the sarcolemma in three different mouse models of Duchenne muscular dystrophy (DMD)...
November 22, 2018: Skeletal Muscle
Andrew N Billin, Samuel E Honeycutt, Alan V McDougal, Jaclyn P Kerr, Zhe Chen, Johannes M Freudenberg, Deepak K Rajpal, Guizhen Luo, Henning Fritz Kramer, Robert S Geske, Frank Fang, Bert Yao, Richard V Clark, John Lepore, Alex Cobitz, Ram Miller, Kazunori Nosaka, Aaron C Hinken, Alan J Russell
BACKGROUND: In muscular dystrophy and old age, skeletal muscle repair is compromised leading to fibrosis and fatty tissue accumulation. Therefore, therapies that protect skeletal muscle or enhance repair would be valuable medical treatments. Hypoxia-inducible factors (HIFs) regulate gene transcription under conditions of low oxygen, and HIF target genes EPO and VEGF have been associated with muscle protection and repair. We tested the importance of HIF activation following skeletal muscle injury, in both a murine model and human volunteers, using prolyl hydroxylase inhibitors that stabilize and activate HIF...
November 13, 2018: Skeletal Muscle
Masahiro Iwata, Davis A Englund, Yuan Wen, Cory M Dungan, Kevin A Murach, Ivan J Vechetti, Christopher B Mobley, Charlotte A Peterson, John J McCarthy
BACKGROUND: The tetracycline-responsive system (Tet-ON/OFF) has proven to be a valuable tool for manipulating gene expression in an inducible, temporal, and tissue-specific manner. The purpose of this study was to create and characterize a new transgenic mouse strain utilizing the human skeletal muscle α-actin (HSA) promoter to drive skeletal muscle-specific expression of the reverse tetracycline transactivator (rtTA) gene which we have designated as the HSA-rtTA mouse. METHODS: To confirm the HSA-rtTA mouse was capable of driving skeletal muscle-specific expression, we crossed the HSA-rtTA mouse with the tetracycline-responsive histone H2B-green fluorescent protein (H2B-GFP) transgenic mouse in order to label myonuclei...
October 27, 2018: Skeletal Muscle
Andrea Iskenderian, Nan Liu, Qingwei Deng, Yan Huang, Chuan Shen, Kathleen Palmieri, Robert Crooker, Dianna Lundberg, Niksa Kastrapeli, Brian Pescatore, Alla Romashko, John Dumas, Robert Comeau, Angela Norton, Jing Pan, Haojing Rong, Katayoun Derakhchan, David E Ehmann
BACKGROUND: Myostatin antagonists are being developed as therapies for Duchenne muscular dystrophy due to their strong hypertrophic effects on skeletal muscle. Engineered follistatin has the potential to combine the hypertrophy of myostatin antagonism with the anti-inflammatory and anti-fibrotic effects of activin A antagonism. METHODS: Engineered follistatin was administered to C57BL/6 mice for 4 weeks, and muscle mass and myofiber size was measured. In the mdx model, engineered follistatin was dosed for 12 weeks in two studies comparing to an Fc fusion of the activin IIB receptor or an anti-myostatin antibody...
October 27, 2018: Skeletal Muscle
Yeh Siang Lau, Li Xu, Yandi Gao, Renzhi Han
BACKGROUND: Histological assessment of skeletal muscle sections is important for the research of muscle physiology and diseases. Quantifiable measures of skeletal muscle often include mean fiber diameter, fiber size distribution, and centrally nucleated muscle fibers. These parameters offer insights into the dynamic adaptation of skeletal muscle cells during repeated cycles of degeneration and regeneration associated with many muscle diseases and injuries. Computational programs designed to obtain these parameters would greatly facilitate such efforts and offer significant advantage over manual image analysis, which is very labor-intensive and often subjective...
October 18, 2018: Skeletal Muscle
Evelyne M Houang, Yuk Y Sham, Frank S Bates, Joseph M Metzger
The scientific premise, design, and structure-function analysis of chemical-based muscle membrane stabilizing block copolymers are reviewed here for applications in striated muscle membrane injury. Synthetic block copolymers have a rich history and wide array of applications from industry to biology. Potential for discovery is enabled by a large chemical space for block copolymers, including modifications in block copolymer mass, composition, and molecular architecture. Collectively, this presents an impressive chemical landscape to leverage distinct structure-function outcomes...
October 10, 2018: Skeletal Muscle
Muriel Sébastien, Benoit Giannesini, Perrine Aubin, Julie Brocard, Mathilde Chivet, Laura Pietrangelo, Simona Boncompagni, Christophe Bosc, Jacques Brocard, John Rendu, Sylvie Gory-Fauré, Annie Andrieux, Anne Fourest-Lieuvin, Julien Fauré, Isabelle Marty
BACKGROUND: The skeletal muscle fiber has a specific and precise intracellular organization which is at the basis of an efficient muscle contraction. Microtubules are long known to play a major role in the function and organization of many cells, but in skeletal muscle, the contribution of the microtubule cytoskeleton to the efficiency of contraction has only recently been studied. The microtubule network is dynamic and is regulated by many microtubule-associated proteins (MAPs). In the present study, the role of the MAP6 protein in skeletal muscle organization and function has been studied using the MAP6 knockout mouse line...
September 19, 2018: Skeletal Muscle
Yuan Qiao, Menglin Cong, Jianmin Li, Hao Li, Zhenzhong Li
BACKGROUND: The formation of intrafusal muscle (IM) fibers and their contact with afferent proprioceptive axons is critical for construction, function, and maintenance of the stretch reflex. Many factors affect the formation of IM fibers. Finding new factors and mechanisms of IM fiber formation is essential for the reconstruction of stretch reflex arc after injury. METHODS: We established a coculture system of organotypic dorsal root ganglion (DRG) explants and dissociated skeletal muscle (SKM) cells...
September 15, 2018: Skeletal Muscle
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