Project description:Gene expression changes induced by acute skeletal muscle unloading, which leads to physiological changes including muscle atrophy, fibre-type switching, and loss of ability to transition between lipid and glucose as energy source (metabolic inflexibility), was investigated by hind-limb suspension (HLS) treatment of Male ICR mice (28â32 g body wt; Harlan, Indianapolis, IN). Agilent Whole Mouse Genome Oligo Microarrays were utilised to examine the effects of HLS on mRNA expression profiles of the soleus muscle and the gastrocnemius muscle in the hindlimbs of freely ambulating control and 24h HLS treated mice. Experiment Overall Design: Five independent biological replicates of this experiment (Control and HLS) were carried out.
Project description:Gene expression changes induced by acute skeletal muscle unloading, which leads to physiological changes including muscle atrophy, fibre-type switching, and loss of ability to transition between lipid and glucose as energy source (metabolic inflexibility), was investigated by hind-limb suspension (HLS) treatment of Male ICR mice (28–32 g body wt; Harlan, Indianapolis, IN). Agilent Whole Mouse Genome Oligo Microarrays were utilised to examine the effects of HLS on mRNA expression profiles of the soleus muscle and the gastrocnemius muscle in the hindlimbs of freely ambulating control and 24h HLS treated mice. Keywords: treatment vs control, tissue type comparison
Project description:To understand the role of LSD1 in transcriptional regulation in muscle under glucocorticoid stress, RNA-seq analyses of gastrocnemius and soleus muscles of skeletal muscle-specific LSD1 KO mice (LSD1-mKO mice) and WT mice after dexamethasone were carried out. We found that LSD1 inhibition led to increased expression of muscle atrophy associated genes and slow fiber genes in gastrocnemius muscle but not in soleus muscle.
Project description:Rodent hind limb unloading was used as a model for reduced muscle activity and eventual atrophy. After a 10 day period of unloading, mice in this study were “reloaded” for 3 days and regained use of their hind limbs. We report the application of Next-generation sequencing (NGS) technology for high-throughput profiling of mRNA in soleus muscle of adult (6 mo) and aged (22-24 mo) mice. Our goal was to determine the effects of hind limb unloading and reloading on mRNA profiles in soleus muscle and compare between adult and aged mice. We find that there are distinct response in the profile of fatty acid oxidation, TCA cycle, ETC oxidative phosphorylation gene expression patterns in response to unloading and reloading. The repsonses are generally simialr between young and old mice.
Project description:Adverse effects of statins include skeletal muscle toxicity; Type II glycolytic fibers are more senstive to statin damage; exercise exacerbates statin muscle degeneration. We used a well-characterized rat model of statin-induced muscle degeneration, at which 1.0 mg/kg/day (high dose) cerivastatin produces mild to moderate histological degeneration. We used microarrays to detail the global programme of gene expression underlying cerivastatin effects on rat gastrocnemius and soleus muscles, as well as the effect of cerivastatin combined with treadmill exercise. We identified distinct classes of up- and down-regulated genes during this process. Experiment Overall Design: We treated female SD rats with vehicle or 3 doses of cerivastatin (0.1, 0.5, 1.0 mg/kg/day) for 14 days, plus or minus 5 days/week of exercise on treadmills (20 min/day at 20 m/min). Gastrocnemius and soleus muscle samples were harvested for RNA extraction and hybridization on Affymetrix microarrays. A total of 12 samples were analyzed with 3-4 biological replicates per sample. Our goals were to determine 1) the effect of cerivastatin; 2) the effect of exercise combined with cerivastatin; 3) an explanation for the muscle fiber type sensitivity to statins. Since all doses of cerivastatin had no effect on soleus muscle (PubMed ID: 16141437), we analysed samples from soleus from control and high dose groups only.
Project description:Muscle (M), myotendinous (J) and tendon (T) tissues were isolated from murine wild-type soleus muscle-tendon units. Tissues were either: 1) fractionated prior to LC-MS/MS analysis of the CS and IN fractions; or 2) homogenized prior to LC-MS/MS analysis of the homogenate. Samples were analyzed by Q Exactive (Thermo Scientific).
Project description:To investigate the molecular mechanisms governing the transition of skeletal muscle from atrophy to compensatory regeneration and hypertrophy, we employed a mouse model involving hindlimb unloading and subsequent reloading, conducting a comprehensive analysis of global gene expression using RNA-sequencing (RNA-seq). Gastrocnemius muscle samples were obtained from three groups: control mice, mice subjected to 10 days of hindlimb unloading-induced muscle atrophy, and mice reintroduced to normal cage activity for 1 day following the unloading period (reloading).
Project description:Skeletal muscle atrophy, which is induced by factors such as disuse, spaceflight, certain medications, neurological disorders, and malnutrition, is a global health issue lacking effective treatment. Hindlimb unloading is a commonly used model for muscle atrophy. However, the underlying mechanism of muscle atrophy induced by hindlimb unloading remains unclear, particular from the perspective of myocyte proteome and metabolism. We first used mass spectrometry for proteomic sequencing and untargeted metabolomics to analyze soleus muscle changes in rats with hindlimb unloading. The study found 1052 proteins and 377 metabolites (with MS2 name) differentially expressed between HU group and CON group. Proteins like ACTN3, MYH4, MYBPC2, and MYOZ1, typically found in fast-twitch muscles, were upregulated, along with metabolism-related proteins GLUL, GSTM4, and NDUFS4. Metabolites arachidylcarnitine and 7,8-dihydrobiopterin, and pathways like histidine, taurine, and hypotaurine metabolism were linked to muscle atrophy. Protein and metabolism joint analysis revealed that some pathways such as glutathione metabolism, ferroptosis and lysosome pathways were likely to be involved in soleus atrophy. In this study, we have applied integrated deep proteomic and metabolomic analysis. The upregulation of proteins which are expressed in fast-twitch fibers indicated the conversion of slow-twitch fibers to fast-twitch fibers under HU. Some metabolism-related proteins have been screened out. Besides, some differentially abundant metabolites and pathways revealed the important role of metabolism in the muscle atrophy of soleus. Our study provides insights into the pathogenesis and treatment of muscle atrophy that results from unloading by integrating the proteomics and metabolomics of soleus muscles.