Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptional pathways associated with skeletal muscle disuse atrophy in humans

ABSTRACT: Disuse atrophy is a common clinical phenomenon which significantly impacts muscle function and activities of daily living. In this study, we did expression profiling to identify transcriptional pathways associated with muscle remodeling in a clinical model of disuse. Keywords: Differentiation design 28 Skeletal muscle biopsies from the medial gastrocnemius in patients with an ankle fracture (4 patients, 8 profiles) and from healthy volunteers (2 subjects, 4 profiles) subjected to 4-11 days of mobilization, as well as from the non-immobilized contralateral legs (16 profiles).

ORGANISM(S): Homo sapiens

SUBMITTER: Eric Hoffman

PROVIDER: E-GEOD-8872 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Publications

Transcriptional pathways associated with skeletal muscle disuse atrophy in humans.

Chen Yi-Wen YW Gregory Chris M CM Scarborough Mark T MT Shi Rongye R Walter Glenn A GA Vandenborne Krista K

Physiological genomics 20070905 3

Disuse atrophy is a common clinical phenomenon that significantly impacts muscle function and activities of daily living. The purpose of this study was to implement genome-wide expression profiling to identify transcriptional pathways associated with muscle remodeling in a clinical model of disuse. Skeletal muscle biopsies were acquired from the medial gastrocnemius in patients with an ankle fracture and from healthy volunteers subjected to 4-11 days of cast immobilization. We identified 277 mis ...[more]

PMID: 17804603

Similar Datasets

Effect of 6-day disuse on transcriptome in human soleus and vastus lateralis muscles

Project description:This study assessed the effects of weekly disuse (dry immersion; 10 males) on the strength and aerobic performance of the ankle plantar flexors and knee extensors, mitochondrial function in permeabilized muscle fibers, and the proteomic (quantitative mass spectrometry-based analysis) and transcriptomic (RNA-sequencing) profiles of the soleus muscle and vastus lateralis muscle. Dry immersion-induced decreases in maximal voluntary contraction in both muscles were comparable and occurred without a decrease in the relative content of contractile proteins, which appears to be due to disruption of neuromuscular mechanisms rather than a decrease in muscle mass. The decrease in maximum ADP-stimulated mitochondrial respiration was also comparable in both muscles and occurred without a decrease in the relative content of mitochondrial proteins/respiratory enzymes, which appears to be associated with dysregulation of respiration. Meanwhile changes in the transcriptome were significantly more pronounced (2.5–4 times, in terms of number of differentially expressed genes) in the “slow” soleus muscle than in the vastus lateralis muscle. This suggests that longer-term disuse will lead to a change (primarily a decrease) in the relative content of a number of highly abundant proteins in Sol and an accelerated decline in the functional capacity of the ankle plantar flexors.

2024-09-08 | GSE271607 | GEO

Molecular Signatures of Muscle Rehabilitation After Limb Disuse

Project description:We have identified the molecular (transcriptional) signatures associated with muscle remodeling in response to rehabilitation in a patient cohort. Subjects with a closed malleolus fracture treated conservatively with 6 weeks of cast immobilization are recruited. Then subjects are enrolled in a 6 weeks structured rehabilitation program focusing on progressive resistance training of the ankle plantar flexor muscles. Phenotypic measurements are performed before (pre-rehab), during (mid-rehab, 3 weeks) and immediately after (post-rehab, 6 weeks) the rehabilitation intervention. The maximal cross-sectional area (muscle size) and peak torque (muscle strength) are quantified using isometric and isokinetic tests in combination with 3D-magnetic resonance imaging. Ankle plantar flexor muscle size and strength measurements are also performed on the uninvolved limb (serves as a control) at 4 months post-immobilization. Measurements are also acquired from the contralateral leg, which serves as an internal control.

2017-08-31 | GSE45462 | GEO

A Non-invasive Mouse Model That Recapitulates Disuse-Induced Muscle Atrophy in Immobilized Patients

Project description:Disuse muscle atrophy occurs consequent to prolonged limb immobility or bed rest, which represents an unmet medical need. As existing animal models of limb immobilization often cause skin erosion, edema, and other untoward effects, we here report an alternative method via thermoplastic immobilization of hindlimbs in mice. While significant decreases in the weight and fiber size were noted after 7 days of immobilization, no apparent skin erosion or edema was found. To shed light onto the molecular mechanism underlying this muscle wasting, we performed the next-generation sequencing analysis of gastrocnemius muscles from immobilized versus non-mobilized legs. Among a total of 55,487 genes analyzed, 787 genes were differentially expressed (> 4-fold; 454 and 333 genes up- and down-regulated, respectively), which included genes associated with muscle tissue development, muscle system process, protein digestion and absorption, and inflammation-related signaling. To the best our knowledge, this is the first study that used RNA-seq to reveal changes in the skeletal muscle transcriptome profiling in response to disuse atrophy without denervation. From a clinical perspective, this model may help understand the molecular/cellular mechanism that drives muscle disuse and identify therapeutic strategies for this debilitating disease.

2023-12-06 | GSE237537 | GEO

Multidirectional effect of low-intensity electrical myostimulation on gene expression and phenotype in thigh and calf muscles after one week of disuse

Project description:Low-intensity neuromuscular electrical stimulation (NMES) is often used as an alternative to exercise and high-intensity electrical stimulation to prevent the loss of muscle mass, strength, and endurance in spaceflight and in patients with severe chronic diseases. This study assessed the efficiency of low-intensity (~10% of maximal voluntary contraction) combined (low- and high-frequency) electrical stimulation in preventing the negative effects of weekly disuse (dry immersion without [DI, see a related dataset GSE271607] and with [DI+NMES] daily stimulation; 10 males in each group) on the strength and aerobic performance of the ankle plantar flexors and knee extensors, mitochondrial function in permeabilized muscle fibers, and the proteomic (quantitative mass spectrometry-based analysis) and transcriptomic (RNA-sequencing) profiles of the soleus muscle and vastus lateralis muscle. Application of electrical stimulation during dry immersion prevented a decrease in the maximal strength and a slight reduction in aerobic performance of knee extensors, as well as a decrease in maximal ADP-stimulated mitochondrial respiration and changes in the expression of genes encoding mitochondrial, extracellular matrix, and membrane proteins in the vastus lateralis muscle. In contrast, for the ankle plantar flexors/soleus muscle, electrical stimulation had a positive effect only on maximal mitochondrial respiration, but accelerated the decline in the maximal strength and muscle fiber cross-sectional area, which appears to be associated with the activation of genes regulating the inflammatory response. The data obtained open up broad prospects for the use of low-intensity combined electrical stimulation to prevent the negative effects of disuse for “mixed” muscles, meanwhile, the optimization of the stimulation protocol is required for “slow” muscles.

2024-09-08 | GSE271606 | GEO

Differentially expressed genes during disuse atrophy.

Project description:To identify atrophy genes directly targeted by Bcl-3 transactivator at a genome wide level, we performed whole transcript expression array and ChIP-seq for muscles from weight bearing or 5-day hind limb unloaded mice. Genes that showed increased expression with unloading and a Bcl-3 peak in the promoter (from ChIP-seq data) were considered as Bcl-3 direct targets during disuse atrophy. Using ChIP array, we identified 241 direct targets for Bcl-3. Our data describe Bcl-3 as a global regulator both of the proteolysis and the change in energy metabolism that are essential components of muscle atrophy due to disuse. Disuse skeletal muscle atrophy was induced by hind limb unloading. Weight bearing (WB) or 5-day hind limb unloaded (HU) muscles were harvested for total RNA isolation and processed for whole transcript expression profiling. We chose to examine gene expression and Bcl-3 binding from 5-day unloaded muscles because our previous time course study of disuse atrophy suggested that most genes are differentially regulated at this time point, and thus, would best represent the time for Bcl-3 binding to the gene targets of the NF-kB transcriptional network.

2012-11-10 | E-GEOD-40578 | biostudies-arrayexpress

Acute molecular responses to lengthening vs shortening muscle contractions

Project description:To help elucidate mechanistic differences between lengthening and shortening muscle contractions we compared changes in gene expression within 24 h of an acute bout of each type of contraction in the quadriceps. Three healthy young men performed shortening contractions with one leg while the contralateral leg performed lengthening contractions. Biopsies were taken from both legs before exercise, 3, 6, and 24 h afterwards. Expression profiling was performed using a custom-made Affymetrix MuscleChip containing probesets of approximately 3,300 known genes and ESTs expressed in skeletal muscle. We identified 49 genes differentially regulated between the lengthening and shortening contractions. Using unsupervised hierarchical clustering, we identified four distinct clusters, three of which corresponded to unique functional categories (protein synthesis, stress response/early growth, and sarcolemmal structure). The results suggest distinct molecular pathways as early as 3 h post exercise. The molecular differences might contribute to mechanisms underlying the physiological adaptations seen with training using the two modes of exercise. Keywords: Time Series Design The hypothesis of the current study was that genes involved in hypertrophy will be differentially regulated between the two types of contractions.

2007-03-27 | E-GEOD-7286 | biostudies-arrayexpress

Transcriptional pathways associated with skeletal muscle disuse atrophy in humans

Project description:Disuse atrophy is a common clinical phenomenon which significantly impacts muscle function and activities of daily living. In this study, we did expression profiling to identify transcriptional pathways associated with muscle remodeling in a clinical model of disuse. Keywords: Differentiation design

2007-08-28 | GSE8872 | GEO

Response of multiple genes to a chronic dose of corticosteroids in rat muscles

Project description:Synthetic glucocorticoids are used therapeutically for a variety of conditions. Both the efficacy and toxicity of corticosteroids arise from their pharmacologically exaggerated effects on target and non-target tissues. For example, beneficial effects deriving from inhibition of the immune system are accompanied by toxic side effects that include hyperglycemia, dyslipidaemia, muscle wasting, fatty liver, and an increased risk of atherosclerosis. Our previous time series analyzing the gene expression responses following a single bolus dose of methylprednisolone (MPL) provided interesting insight into the genomic responses of liver, skeletal muscle and kidney to corticosteroids. One objective with such extensive gene array time series data is to cluster genes into groups with common mechanisms of regulation. These clusters can be used to construct biologically rational models of the cascade of events that result in broad systemic phenomena such as diabetes, with the ultimate aim of therapeutic intervention at specific steps within the cascade Keywords: Time-Series We analyze the two time series profiles with the intent of seeking ways to use the two profiles in tandem for clustering. The acute profiles were generated by sacrificing animals following a single acute dose of MP [7]. The time points were: 0.25, 0.5, 0.75, 1, 2, 4, 5, 5.5, 6, 7, 8, 12, 18, 30, 48 and, 72 hours after dosing. The chronic profiles were generated by implanting Alzet mini-osmotic pumps with a constant flow rate [8, 9]. Animals were sacrificed at 6, 10, 13, 18, 24, 36, 48, 72, 96 and 168 hr following implantation.

2006-06-19 | E-GEOD-5101 | biostudies-arrayexpress

Mechanotherapy promotes extracellular matrix remodeling in aged rat muscle recovering from disuse by reprogramming intercellular communication

Project description:A mechanistic understanding of the age-related impairment to skeletal muscle regrowth following disuse atrophy as well as therapies to augment recovery in the aged are currently lacking. Mechanotherapy in the form of cyclic compressive loading has been shown to benefit skeletal muscle under a variety of paradigms, but not during the recovery from disuse in aged muscle. To determine whether mechanotherapy promotes extracellular matrix (ECM) remodeling, a critical aspect of muscle recovery after atrophy, we performed single cell RNA sequencing (scRNA-seq) of gastrocnemius muscle cell populations, stable isotope tracing of intramuscular collagen, and histology of the ECM in adult and aged rats recovering from disuse, with and without mechanotherapy. ECM remodeling-related gene expression in fibro-adipose progenitor cells (FAPs) was absent in aged compared to adult muscle following 7 days of recovery, and instead were enriched in chemoattractant genes. There was a significantly lower expression of genes related to phagocytic activity in aged macrophages during recovery, despite enriched chemokine gene expression of numerous stromal cell populations, including FAPs and endothelial cells. Mechanotherapy reprogrammed the transcriptomes of both FAPs and macrophages in aged muscle recovering from disuse to restore ECM-and phagocytosis-related gene expression, respectively. Stable isotope labeling of intramuscular collagen and histological evaluation confirmed mechanotherapy-mediated remodeling of the ECM in aged muscle recovering from disuse. In summary, our results highlight mechanisms underlying age-related impairments during the recovery from disuse atrophy and promote mechanotherapy as an intervention that reprograms the muscle transcriptional environment more similar to that of adult skeletal muscle.

2022-03-31 | GSE184413 | GEO

Proteomic identification of seasonally expressed proteins contributing to heart function and the avoidance of skeletal muscle disuse atrophy in a hibernating mammal

Project description:Hibernation in mammals such as the thirteen-lined ground squirrel (Ictidomys tridecemlineatus) takes place over 4 to 6 months and is characterized by multi-day bouts of hypothermic torpor (5-7 °C core body temperature) that are regularly interrupted every 1-2 weeks by brief (12-24 hour) normothermic arousal periods called interbout arousals. The goal of our work was to identify the molecular mechanisms which underlie the hibernator’s ability to preserve heart function and avoid the deleterious effects of skeletal muscle disuse atrophy over prolonged periods of inactivity, starvation, and near-freezing body temperatures. To achieve this goal, we performed organelle enrichment of heart and skeletal muscle at five seasonal time points followed by LC-MS-based label-free quantitative proteomics. In both organs we saw a dramatic increase in levels of many proteins as ground squirrels transition from an active state in September to a pre-hibernation state in October. Interestingly, seasonal abundance patterns also identified new candidates for mitigating disuse atrophy in skeletal muscle which include higher levels of DHRS7C, SRL, and RTN2 in December-January torpid, IBA, and March active animals; and higher March active levels of TRIM72 and MPZ. Elevation of these proteins prompted us to perform an ex vivo contractile mechanics analysis of both type 1 (soleus) and type 2 (extensor digitorum longus) muscles in fall active, torpid, and spring active animals. Consistent with our hypotheses, both muscle types showed no deleterious effects despite several months of sedentary activity that would normally result in reduced muscle performance in non-hibernating mammals. An increased understanding of protein expression in natural hibernators may enable novel therapeutic strategies to treat human health concerns such as muscle disuse atrophy and heart disease.

2023-12-21 | PXD044532 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data